Abstract
Background
Pattern recognition receptors (PRRs) are crucial immune modulators that orchestrate innate and adaptive immune systems for the regulation of inflammatory responses. Several PRR families and their ligands associated with immune modulation have been identified, which promoted the development of natural and synthetic PRR agonistic ligands as adjuvants in immunotherapy applications. However, conventional adjuvants are mainly based on small molecules, peptides, lipids, and oligonucleotides, which suffer from unfavorable drug-like properties for in vivo applications, including vulnerability to biodegradation, undesirable pharmacokinetic profiles, and poor cellular uptake. Nanoparticle formulation is a promising approach for addressing the issues with conventional adjuvants.
Area covered
This review aims to provide a broad understanding of nano-adjuvants utilized in cancer immunotherapy. For this purpose, we introduce the background, summarize the current knowledge on PRRs and their ligands for some representative classes, and highlight various nanoparticle platforms that are utilized to construct nano-adjuvants in cancer immunotherapy. We also discuss some design considerations for optimal nano-adjuvant formulations with potent adjuvant activity and desired in vivo performance.
Expert opinion
Nanoparticles provide a robust and versatile platform to shape conventional adjuvants into more drug-like formulations, and the preclinical studies and clinical trials have demonstrated their potential in cancer immunotherapy. The emergence of cancer immunotherapy in clinics will fuel continuous efforts toward highly efficient nano-adjuvant systems that can strongly boost the antitumor immune responses in cancer immunotherapy. The accumulated knowledge gained through the progress will provide important insights into optimal nano-adjuvant formulations and potentially guide their clinical translation.
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References
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) in Molecular Biology of the Cell. 4th edition
Albin TJ, Tom JK, Manna S, Gilkes AP, Stetkevich SA, Katz BB, Supnet M, Felgner J, Jain A, Nakajima R, Jasinskas A, Zlotnik A, Pearlman E, Davies DH, Felgner PL, Burkhardt AM, Esser-Kahn AP (2019) Linked toll-like receptor triagonists stimulate distinct, combination-dependent Innate Immune responses. ACS Cent Sci 5:1137–1145
Allen IC, Tekippe EM, Woodford R-MT, Uronis JM, Holl EK, Rogers AB, Herfarth HH, Jobin C, Ting JP-Y (2010) The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med 207:1045–1056
Allen IC, Wilson JE, Schneider M, Lich JD, Roberts RA, Arthur JC, Woodford R-MT, Davis BK, Uronis JM, Herfarth HH (2012) NLRP12 suppresses colon inflammation and tumorigenesis through the negative regulation of noncanonical NF-κB signaling. Immunity 36:742–754
Amarante-Mendes GP, Adjemian S, Branco LM, Zanetti LC, Weinlich R, Bortoluci KR (2018) Pattern recognition receptors and the host cell death molecular machinery. Front Immunol 9
Andrade WA, Souza Mdo C, Ramos-Martinez E, Nagpal K, Dutra MS, Melo MB, Bartholomeu DC, Ghosh S, Golenbock DT, Gazzinelli RT (2013) Combined action of nucleic acid-sensing toll-like receptors and TLR11/TLR12 heterodimers imparts resistance to Toxoplasma gondii in mice. Cell Host Microbe 13:42–53
Anwar MA, Shah M, Kim J, Choi S (2019) Recent clinical trends in toll-like receptor targeting therapeutics. Med Res Rev 39:1053–1090
Azuma M, Takeda Y, Nakajima H, Sugiyama H, Ebihara T, Oshiumi H, Matsumoto M, Seya T (2016) Biphasic function of TLR3 adjuvant on tumor and spleen dendritic cells promotes tumor T cell infiltration and regression in a vaccine therapy. Oncoimmunology 5:e1188244
Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811
Bartneck M, Keul HA, Singh S, Czaja K, Bornemann J, Bockstaller M, Moeller M, Zwadlo-Klarwasser G, Groll J (2010) Rapid uptake of gold nanorods by primary human blood phagocytes and immunomodulatory effects of surface chemistry. ACS Nano 4:3073–3086
Barton GM, Medzhitov R (2003) Toll-like receptor signaling pathways. Sci (New York N Y) 300:1524–1525
Bayyurt B, Tincer G, Almacioglu K, Alpdundar E, Gursel M, Gursel I (2017) Encapsulation of two different TLR ligands into liposomes confer protective immunity and prevent tumor development. J Controlled Release: Official J Controlled Release Soc 247:134–144
Belling JN, Jackman JA, Yorulmaz Avsar S, Park JH, Wang Y, Potroz MG, Ferhan AR, Weiss PS, Cho NJ (2016) Stealth Immune Properties of Graphene Oxide enabled by surface-bound complement factor H. ACS Nano 10:10161–10172
Besch R, Poeck H, Hohenauer T, Senft D, Häcker G, Berking C, Hornung V, Endres S, Ruzicka T, Rothenfusser S (2009) Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon–independent apoptosis in human melanoma cells. J Clin Investig 119:2399–2411
Bhoopathi P, Quinn BA, Gui Q, Shen X-N, Grossman SR, Das SK, Sarkar D, Fisher PB, Emdad L (2014) Pancreatic cancer–specific cell death induced in vivo by cytoplasmic-delivered polyinosine–polycytidylic acid. Cancer Res 74:6224–6235
Boks MA, Bruijns SCM, Ambrosini M, Kalay H, Van Bloois L, Storm G, Gruijl TD, Van Kooyk Y (2015) In situ delivery of Tumor Antigen– and adjuvant-loaded liposomes boosts Antigen-Specific T-Cell responses by human dermal dendritic cells. J Invest Dermatology 135:2697–2704
Brackett CM, Kojouharov B, Veith J, Greene KF, Burdelya LG, Gollnick SO, Abrams SI, Gudkov AV (2016) Toll-like receptor-5 agonist, entolimod, suppresses metastasis and induces immunity by stimulating an NK-dendritic-CD8 + T-cell axis. Proc Natl Acad Sci USA 113:E874–883
Brown GD (2006) Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat Rev Immunol 6:33–43
Camacho AI, Da Costa Martins R, Tamayo I, De Souza J, Lasarte JJ, Mansilla C, Esparza I, Irache JM, Gamazo C (2011) Poly(methyl vinyl ether-co-maleic anhydride) nanoparticles as innate immune system activators. Vaccine 29:7130–7135
Cao P, Han FY, Grøndahl L, Xu ZP, Li L (2020) Enhanced oral vaccine efficacy of polysaccharide-coated calcium phosphate nanoparticles. ACS Omega 5:18185–18197
Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J (2003) Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J Exp Med 197:403–411
Casals C, García-Fojeda B, Minutti CM (2019) Soluble defense collagens: sweeping up immune threats. Mol Immunol 112:291–304
Cen X, Zhu G, Yang J, Yang J, Guo J, Jin J, Nandakumar KS, Yang W, Yin H, Liu S, Cheng K (2019) TLR1/2 specific small-molecule agonist suppresses Leukemia Cancer Cell Growth by stimulating cytotoxic T lymphocytes. Adv Sci (Weinheim Baden-Wurttemberg Germany) 6:1802042
Chandra D, Quispe-Tintaya W, Jahangir A, Asafu-Adjei D, Ramos I, Sintim HO, Zhou J, Hayakawa Y, Karaolis DK, Gravekamp C (2014) STING ligand c-di-GMP improves Cancer vaccination against metastatic breast Cancerc-di-GMP improves vaccination against breast Cancer. Cancer Immunol Res 2:901–910
Chan L-P, Wang L-F, Chiang F-Y, Lee K-W, Kuo P-L, Liang C-H (2016) IL-8 promotes HNSCC progression on CXCR1/2-meidated NOD1/RIP2 signaling pathway. Oncotarget 7:61820
Chatzikleanthous D, O’hagan DT, Adamo R (2021) Lipid-based nanoparticles for delivery of Vaccine Adjuvants and Antigens: toward Multicomponent Vaccines. Mol Pharm 18:2867–2888
Chen GY, Shaw MH, Redondo G, Núñez G (2008) The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis. Cancer Res 68:10060–10067
Chen Q, Xu L, Liang C, Wang C, Peng R, Liu Z (2016) Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat Commun 7:13193
Chen X, Zhang Y, Fu Y (2022) The critical role of toll-like receptor-mediated signaling in cancer immunotherapy. Med Drug Discovery 14:100122
Cheng K, Kang Q, Zhao X (2020) Biogenic nanoparticles as immunomodulator for tumor treatment. Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology 12:e1646
Chiba S, Ikushima H, Ueki H, Yanai H, Kimura Y, Hangai S, Nishio J, Negishi H, Tamura T, Saijo S, Iwakura Y, Taniguchi T (2014) Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses. eLife 3:e04177
Chuenchor W, Jin T, Ravilious G, Xiao TS (2014) Structures of pattern recognition receptors reveal molecular mechanisms of autoinhibition, ligand recognition and oligomerization. Curr Opin Immunol 26:14–20
Clements CJ, Griffiths E (2002) The global impact of vaccines containing aluminium adjuvants. Vaccine 20(Suppl 3):S24–33
Coccia M, Collignon C, Hervé C, Chalon A, Welsby I, Detienne S, Van Helden MJ, Dutta S, Genito CJ, Waters NC, Deun KV, Smilde AK, Berg R, Franco D, Bourguignon P, Morel S, Garçon N, Lambrecht BN, Goriely S, Most RV, Didierlaurent AM (2017) Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity. NPJ Vaccines 2:25
Conforti-Andreoni C, Beretta O, Licandro G, Qian HL, Urbano M, Vitulli F, Ricciardi‐Castagnoli P, Mortellaro A (2010) Synergism of NOD2 and NLRP3 activators promotes a unique transcriptional profile in murine dendritic cells. J Leukoc Biol 88:1207–1216
Conlon J, Burdette DL, Sharma S, Bhat N, Thompson M, Jiang Z, Rathinam VA, Monks B, Jin T, Xiao TS, Vogel SN, Vance RE, Fitzgerald KA (2013) Mouse, but not human STING, binds and signals in response to the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid. J Immunol (Baltimore Md : 1950) 190:5216–5225
Corrales L, Glickman LH, Mcwhirter SM, Kanne DB, Sivick KE, Katibah GE, Woo SR, Lemmens E, Banda T, Leong JJ, Metchette K, Dubensky TW Jr, Gajewski TF (2015) Direct activation of STING in the Tumor Microenvironment leads to potent and systemic Tumor regression and immunity. Cell Rep 11:1018–1030
Couturier-Maillard A, Secher T, Rehman A, Normand S, De Arcangelis A, Haesler R, Huot L, Grandjean T, Bressenot A, Delanoye-Crespin A (2013) NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J Clin Investig 123
Cui J, De Rose R, Best JP, Johnston AP, Alcantara S, Liang K, Such GK, Kent SJ, Caruso F (2013) Mechanically tunable, self-adjuvanting nanoengineered polypeptide particles. Advanced materials (Deerfield Beach. Fla) 25:3468–3472
Damiano JS, Oliveira V, Welsh K, Reed JC (2004) Heterotypic interactions among NACHT domains: implications for regulation of innate immune responses. Biochem J 381:213–219
Da Silva CA, Pochard P, Lee CG, Elias JA (2010) Chitin particles are multifaceted immune adjuvants. Am J Respir Crit Care Med 182:1482–1491
Da Silva Correia J, Miranda Y, Austin-Brown N, Hsu J, Mathison J, Xiang R, Zhou H, Li Q, Han J, Ulevitch RJ (2006) Nod1-dependent control of tumor growth. Proceedings of the National Academy of Sciences 103:1840–1845
De Faria PC, Dos Santos LI, Coelho JP, Ribeiro HB, Pimenta MA, Ladeira LO, Gomes DA, Furtado CA, Gazzinelli RT (2014) Oxidized multiwalled carbon nanotubes as antigen delivery system to promote superior CD8(+) T cell response and protection against cancer. Nano Lett 14:5458–5470
Didierlaurent AM, Morel S, Lockman L, Giannini SL, Bisteau M, Carlsen H, Kielland A, Vosters O, Vanderheyde N, Schiavetti F, Larocque D, Van Mechelen M, Garçon N (2009) AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity. Journal of immunology (Baltimore, Md.: 1950) 183:6186–6197
Didierlaurent AM, Laupèze B, Di Pasquale A, Hergli N, Collignon C, Garçon N (2017) Adjuvant system AS01: helping to overcome the challenges of modern vaccines. Expert Rev Vaccines 16:55–63
Diebold SS, Kaisho T, Hemmi H, Akira S, Reis E, Sousa C (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA, vol 303. Science, New York, N.Y., pp 1529–1531
Di Lorenzo A, Bolli E, Tarone L, Cavallo F, Conti L (2020) Toll-Like Receptor 2 at the Crossroad between Cancer Cells, the Immune System, and the Microbiota. International journal of molecular sciences 21
Ding B, Shao S, Yu C, Teng B, Wang M, Cheng Z, Wong KL, Ma P, Lin J (2018) Large-Pore Mesoporous-Silica-Coated Upconversion Nanoparticles as Multifunctional Immunoadjuvants with Ultrahigh Photosensitizer and Antigen Loading Efficiency for Improved Cancer Photodynamic Immunotherapy. Advanced materials (Deerfield Beach, Fla.) 30:e1802479
Ding FX, Wang F, Lu YM, Li K, Wang KH, He XW, Sun SH (2009) Multiepitope peptide-loaded virus-like particles as a vaccine against hepatitis B virus-related hepatocellular carcinoma. Hepatology (Baltimore MD) 49:1492–1502
Domingo GJ, Chauhan HJ, Lessard IA, Fuller C, Perham RN (1999) Self-assembly and catalytic activity of the pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus. Eur J Biochem 266:1136–1146
Drobits B, Holcmann M, Amberg N, Swiecki M, Grundtner R, Hammer M, Colonna M, Sibilia M (2012) Imiquimod clears tumors in mice independent of adaptive immunity by converting pDCs into tumor-killing effector cells. J Clin Invest 122:575–585
Duan S, Xu X, Wang J, Huang L, Peng J, Yu T, Zhou Y, Cheng K, Liu S (2021) TLR1/2 agonist enhances reversal of HIV-1 latency and promotes NK Cell-Induced suppression of HIV-1-Infected autologous CD4(+) T cells. J Virol 95:e0081621
Durán-Lobato M, Carrillo-Conde B, Khairandish Y, Peppas NA (2014) Surface-modified P(HEMA-co-MAA) nanogel carriers for oral vaccine delivery: design, characterization, and in vitro targeting evaluation. Biomacromolecules 15:2725–2734
Dziarski R, Jin YP, Gupta D (1996) Differential activation of extracellular signal-regulated kinase (ERK) 1, ERK2, p38, and c-Jun NH2-terminal kinase mitogen-activated protein kinases by bacterial peptidoglycan. J Infect Dis 174:777–785
El Andaloussi A, Sonabend AM, Han Y, Lesniak MS (2006) Stimulation of TLR9 with CpG ODN enhances apoptosis of glioma and prolongs the survival of mice with experimental brain tumors. Glia 54:526–535
Elion DL, Jacobson ME, Hicks DJ, Rahman B, Sanchez V, Gonzales-Ericsson PI, Fedorova O, Pyle AM, Wilson JT, Cook RS (2018) Therapeutically active RIG-I agonist induces immunogenic Tumor Cell killing in breast cancers. Cancer Res 78:6183–6195
Fan L, Zhou P, Hong Q, Chen AX, Liu GY, Yu KD, Shao ZM (2019) Toll-like receptor 3 acts as a suppressor gene in breast cancer initiation and progression: a two-stage association study and functional investigation. Oncoimmunology 8:e1593801
Fang RH, Kroll AV, Zhang L (2015) Nanoparticle-based manipulation of Antigen-Presenting cells for Cancer Immunotherapy. Small 11:5483–5496
Fang RH, Kroll AV, Gao W, Zhang L (2018) Cell Membrane Coating Nanotechnology. Advanced materials (Deerfield Beach, Fla.) 30:e1706759
Fitzgerald KA, Kagan JC (2020) Toll-like receptors and the control of immunity. Cell 180:1044–1066
Foit L, Thaxton CS (2016) Synthetic high-density lipoprotein-like nanoparticles potently inhibit cell signaling and production of inflammatory mediators induced by lipopolysaccharide binding toll-like receptor 4. Biomaterials 100:67–75
Frank MJ, Khodadoust MS, Czerwinski DK, Haabeth OaW, Chu MP, Miklos DB, Advani RH, Alizadeh AA, Gupta NK, Maeda LS, Reddy SA, Laport GG, Meyer EH, Negrin RS, Rezvani AR, Weng WK, Sheehan K, Faham M, Okada A, Moore AH, Phillips DL, Wapnir IL, Brody JD, Levy R (2020) Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: a phase I/II trial. J Exp Med 217
Franzoni G, Anfossi A, De Ciucis CG, Mecocci S, Carta T, Dei Giudici S, Fruscione F, Zinellu S, Vito G, Graham SP, Oggiano A, Chessa B, Razzuoli E (2021) Targeting toll-like receptor 2: polarization of Porcine Macrophages by a Mycoplasma-Derived Pam2cys Lipopeptide. Vaccines 9.
Furukawa A, Kamishikiryo J, Mori D, Toyonaga K, Okabe Y, Toji A, Kanda R, Miyake Y, Ose T, Yamasaki S, Maenaka K (2013) Structural analysis for glycolipid recognition by the C-type lectins Mincle and MCL. Proc Natl Acad Sci USA 110:17438–17443
Fytianos K, Chortarea S, Rodriguez-Lorenzo L, Blank F, Von Garnier C, Petri-Fink A, Rothen-Rutishauser B (2017) Aerosol Delivery of Functionalized Gold Nanoparticles Target and activate dendritic cells in a 3D Lung Cellular Model. ACS Nano 11:375–383
Garçon N, Van Mechelen M (2011) Recent clinical experience with vaccines using MPL- and QS-21-containing adjuvant systems. Expert Rev Vaccines 10:471–486
Garrett WS, Chen L-M, Kroschewski R, Ebersold M, Turley S, Trombetta S, Galán JE, Mellman I (2000) Developmental control of endocytosis in dendritic cells by Cdc42. Cell 102:325–334
Gause KT, Wheatley AK, Cui J, Yan Y, Kent SJ, Caruso F (2017) Immunological principles guiding the Rational design of particles for Vaccine Delivery. ACS Nano 11:54–68
Geijtenbeek TB, Gringhuis SI (2009) Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol 9:465–479
Getts DR, Shea LD, Miller SD, King NJ (2015) Harnessing nanoparticles for immune modulation. Trends Immunol 36:419–427
Ghaffar KA, Giddam AK, Zaman M, Skwarczynski M, Toth I (2014) Liposomes as nanovaccine delivery systems. Curr Top Med Chem 14:1194–1208
Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C, Vermaelen K, Panaretakis T, Mignot G, Ullrich E, Perfettini JL, Schlemmer F, Tasdemir E, Uhl M, Génin P, Civas A, Ryffel B, Kanellopoulos J, Tschopp J, André F, Lidereau R, Mclaughlin NM, Haynes NM, Smyth MJ, Kroemer G, Zitvogel L (2009) Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 15:1170–1178
Goubau D, Deddouche S, Sousa E CR (2013) Cytosolic sensing of viruses. Immunity 38:855–869
Gowen BB, Wong MH, Jung KH, Sanders AB, Mitchell WM, Alexopoulou L, Flavell RA, Sidwell RW (2007) TLR3 is essential for the induction of protective immunity against Punta Toro Virus infection by the double-stranded RNA (dsRNA), poly(I:C12U), but not Poly(I:C): differential recognition of synthetic dsRNA molecules. Journal of immunology (Baltimore, Md.: 1950) 178:5200–5208
Guo L, Yan DD, Yang D, Li Y, Wang X, Zalewski O, Yan B, Lu W (2014) Combinatorial photothermal and immuno cancer therapy using chitosan-coated hollow copper sulfide nanoparticles. ACS Nano 8:5670–5681
Guy B (2007) The perfect mix: recent progress in adjuvant research. Nat Rev Microbiol 5:505–517
Hafner AM, Corthésy B, Merkle HP (2013) Particulate formulations for the delivery of poly(I:C) as vaccine adjuvant. Adv Drug Deliv Rev 65:1386–1399
Hamid O, Solomon JC, Scotland R, Garcia M, Sian S, Ye W, Groshen SL, Weber JS (2007) Alum with interleukin-12 augments immunity to a melanoma peptide vaccine: correlation with time to relapse in patients with resected high-risk disease. Clin cancer Research: Official J Am Association Cancer Res 13:215–222
Han S, Wang W, Wang S, Yang T, Zhang G, Wang D, Ju R, Lu Y, Wang H, Wang L (2021) Tumor microenvironment remodeling and tumor therapy based on M2-like tumor associated macrophage-targeting nano-complexes. Theranostics 11:2892–2916
Harding SM, Benci JL, Irianto J, Discher DE, Minn AJ, Greenberg RA (2017) Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature 548:466–470
He Y, Hara H, Núñez G (2016) Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci 41:1012–1021
Heidegger S, Kreppel D, Bscheider M, Stritzke F, Nedelko T, Wintges A, Bek S, Fischer JC, Graalmann T, Kalinke U, Bassermann F, Haas T, Poeck H (2019) RIG-I activating immunostimulatory RNA boosts the efficacy of anticancer vaccines and synergizes with immune checkpoint blockade. EBioMedicine 41:146–155
Hooy RM, Massaccesi G, Rousseau KE, Chattergoon MA, Sohn J (2020) Allosteric coupling between Mn2 + and dsDNA controls the catalytic efficiency and fidelity of cGAS. Nucleic Acids Res 48:4435–4447
Horning KJ, Caito SW, Tipps KG, Bowman AB, Aschner M (2015) Manganese is essential for neuronal health. Annu Rev Nutr 35:71–108
Hornung V, Latz E (2010) Intracellular DNA recognition. Nat Rev Immunol 10:123–130
Hu HG, Li YM (2020) Emerging adjuvants for Cancer Immunotherapy. Front Chem 8:601
Hu HG, Wu JJ, Zhang BD, Li WH, Li YM (2020) Pam(3)CSK(4)-CDG(SF) augments Antitumor Immunotherapy by synergistically activating TLR1/2 and STING. Bioconjug Chem 31:2499–2503
Huang B, Zhao J, Li H, He K-L, Chen Y, Mayer L, Unkeless JC, Xiong H (2005) Toll-like receptors on Tumor cells facilitate evasion of Immune Surveillance. Cancer Res 65:5009–5014
Huang B, Zhao J, Unkeless JC, Feng ZH, Xiong H (2008) TLR signaling by tumor and immune cells: a double-edged sword. Oncogene 27:218–224
Huber B, Schellenbacher C, Jindra C, Fink D, Shafti-Keramat S, Kirnbauer R (2015) A chimeric 18L1-45RG1 virus-like particle vaccine cross-protects against oncogenic alpha-7 human papillomavirus types. PLoS ONE 10:e0120152
Ibrahim HM, Mohamed AH, Salem ML, Osman GY, Morsi DS (2020) Anti-neoplastic and immunomodulatory potency of co-treatment based on bovine lactoferrin and/or muramyl dipeptide in tumor-bearing mice. Toxicol Res 9:137–147
Ignatz-Hoover JJ, Wang H, Moreton SA, Chakrabarti A, Agarwal MK, Sun K, Gupta K, Wald DN (2015) The role of TLR8 signaling in acute myeloid leukemia differentiation. Leukemia 29:918–926
Inao T, Harashima N, Monma H, Okano S, Itakura M, Tanaka T, Tajima Y, Harada M (2012) Antitumor effects of cytoplasmic delivery of an innate adjuvant receptor ligand, poly(I:C), on human breast cancer. Breast Cancer Res Treat 134:89–100
Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster SJ, Moran AP, Fernandez-Luna JL, Nuñez G (2003) Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease. J Biol Chem 278:5509–5512
Ishii KJ, Coban C, Kato H, Takahashi K, Torii Y, Takeshita F, Ludwig H, Sutter G, Suzuki K, Hemmi H (2006) A toll-like receptor–independent antiviral response induced by double-stranded B-form DNA. Nat Immunol 7:40–48
Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5:987–995
Javaid N, Choi S (2020) Toll-like receptors from the perspective of cancer treatment. Cancers 12:297
Jiang HY, Najmeh S, Martel G, Macfadden-Murphy E, Farias R, Savage P, Leone A, Roussel L, Cools-Lartigue J, Gowing S, Berube J, Giannias B, Bourdeau F, Chan CHF, Spicer JD, Mcclure R, Park M, Rousseau S, Ferri LE (2020) Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis. Protein Cell 11:187–201
Jiang L-J, Zhang N-N, Ding F, Li X-Y, Chen L, Zhang H-X, Zhang W, Chen S-J, Wang Z-G, Li J-M (2011) RA-inducible gene-I induction augments STAT1 activation to inhibit leukemia cell proliferation. Proceedings of the National Academy of Sciences 108:1897–1902
Kang JY, Nan X, Jin MS, Youn SJ, Ryu YH, Mah S, Han SH, Lee H, Paik SG, Lee JO (2009) Recognition of lipopeptide patterns by toll-like receptor 2-Toll-like receptor 6 heterodimer. Immunity 31:873–884
Kaparakis-Liaskos M, Ferrero RL (2015) Immune modulation by bacterial outer membrane vesicles. Nat Rev Immunol 15:375–387
Kato C, Kojima N (2010) SIGNR1 ligation on murine peritoneal macrophages induces IL-12 production through NFκB activation. Glycoconj J 27:525–531
Kawauchi Y, Kuroda Y, Kojima N (2014) Comparison of the carbohydrate preference of SIGNR1 as a phagocytic receptor with the preference as an adhesion molecule. Int Immunopharmacol 19:27–36
Kübler K, Gehrke N, Riemann S, Böhnert V, Zillinger T, Hartmann E, Pölcher M, Rudlowski C, Kuhn W, Hartmann G (2010) Targeted activation of RNA helicase retinoic acid–inducible Gene-I induces proimmunogenic apoptosis of human ovarian Cancer CellsRIG-I promotes immunogenic Tumor Cell Death. Cancer Res 70:5293–5304
Kübler K, Tho Pesch C, Gehrke N, Riemann S, Daßler J, Coch C, Landsberg J, Wimmenauer V, Pölcher M, Rudlowski C (2011) Immunogenic cell death of human ovarian cancer cells induced by cytosolic poly (I: C) leads to myeloid cell maturation and activates NK cells. Eur J Immunol 41:3028–3039
Kelly MG, Alvero AB, Chen R, Silasi D-A, Abrahams VM, Chan S, Visintin I, Rutherford T, Mor G (2006) TLR-4 signaling promotes Tumor Growth and Paclitaxel Chemoresistance in Ovarian Cancer. Cancer Res 66:3859–3868
Kelley N, Jeltema D, Duan Y, He Y (2019) The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci 20
Kenkel J, Ho P, Kongara S, Henning K, Kreder C, Nolin J, Chapin S, Kowanetz M, Alonso M, Ackerman S (2021) (BMJ Specialist Journals,
Khalifehzadeh R, Arami H (2020) The CpG molecular structure controls the mineralization of calcium phosphate nanoparticles and their immunostimulation efficacy as vaccine adjuvants. Nanoscale 12:9603–9615
Kim J, Li WA, Choi Y, Lewin SA, Verbeke CS, Dranoff G, Mooney DJ (2015) Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy. Nat Biotechnol 33:64–72
Kim SC, Song YS, Kim Y-T, Kim YT, Ryu K-S, Gunapalaiah B, Bi D, Bock HL, Park J-S (2011) Human papillomavirus 16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in 15–25 years old healthy korean women. J Gynecologic Oncol 22:67–75
Kingeter LM, Lin X (2012) C-type lectin receptor-induced NF-κB activation in innate immune and inflammatory responses. Cell Mol Immunol 9:105–112
Kishore U, Greenhough TJ, Waters P, Shrive AK, Ghai R, Kamran MF, Bernal AL, Reid KB, Madan T, Chakraborty T (2006) Surfactant proteins SP-A and SP-D: structure, function and receptors. Mol Immunol 43:1293–1315
Kofoed EM, Vance RE (2011) Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity. Nature 477:592–595
Koppolu B, Zaharoff DA (2013) The effect of antigen encapsulation in chitosan particles on uptake, activation and presentation by antigen presenting cells. Biomaterials 34:2359–2369
Koshy ST, Cheung AS, Gu L, Graveline AR, Mooney DJ (2017) Liposomal Delivery Enhances Immune Activation by STING Agonists for Cancer Immunotherapy. Advanced biosystems 1
Koster BD, López González M, Van Den Hout MF, Turksma AW, Sluijter BJ, Molenkamp BG, Van Leeuwen PA, Vosslamber S, Scheper RJ, Van Den Eertwegh AJ, Van Den Tol MP, Jordanova EJ, De Gruijl TD (2021) T cell infiltration on local CpG-B delivery in early-stage melanoma is predominantly related to CLEC9A(+)CD141(+) cDC1 and CD14(+) antigen-presenting cell recruitment. Journal for immunotherapy of cancer 9
Kreuter J, Speiser PP (1976) New adjuvants on a polymethylmethacrylate base. Infect Immun 13:204–210
Krieg AM (2001) Now I know my CpGs. Trends Microbiol 9:249–252
Kuai R, Ochyl LJ, Bahjat KS, Schwendeman A, Moon JJ (2017) Designer vaccine nanodiscs for personalized cancer immunotherapy. Nat Mater 16:489–496
Kufer TA, Sansonetti PJ (2011) NLR functions beyond pathogen recognition. Nat Immunol 12:121–128
Kwon D, Cha BG, Cho Y, Min J, Park EB, Kang SJ, Kim J (2017) Extra-large pore mesoporous silica nanoparticles for directing in vivo M2 macrophage polarization by delivering IL-4. Nano Lett 17:2747–2756
Kwon YJ, Standley SM, Goh SL, Fréchet JM (2005) Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles. J Controlled Release: Official J Controlled Release Soc 105:199–212
Lara PN Jr, Douillard JY, Nakagawa K, Von Pawel J, Mckeage MJ, Albert I, Losonczy G, Reck M, Heo DS, Fan X, Fandi A, Scagliotti G (2011) Randomized phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J Clin Oncology: Official J Am Soc Clin Oncol 29:2965–2971
Larson TA, Joshi PP, Sokolov K (2012) Preventing protein adsorption and macrophage uptake of gold nanoparticles via a hydrophobic shield. ACS Nano 6:9182–9190
Lauw FN, Caffrey DR, Golenbock DT (2005) Of mice and man: TLR11 (finally) finds profilin. Trends Immunol 26:509–511
Lee IH, Kwon HK, An S, Kim D, Kim S, Yu MK, Lee JH, Lee TS, Im SH, Jon S (2012b) Imageable antigen-presenting gold nanoparticle vaccines for effective cancer immunotherapy in vivo. Angewandte Chemie (International ed. in English) 51:8800–8805
Lee J, Li L, Gretz N, Gebert J, Dihlmann S (2012a) Absent in melanoma 2 (AIM2) is an important mediator of interferon-dependent and -independent HLA-DRA and HLA-DRB gene expression in colorectal cancers. Oncogene 31:1242–1253
Lee SW, Song MK, Baek KH, Park Y, Kim JK, Lee CH, Cheong HK, Cheong C, Sung YC (2000) Effects of a hexameric deoxyriboguanosine run conjugation into CpG oligodeoxynucleotides on their immunostimulatory potentials. Journal of immunology (Baltimore, Md.: 1950) 165:3631–3639
Leibundgut-Landmann S, Groß O, Robinson MJ, Osorio F, Slack EC, Tsoni SV, Schweighoffer E, Tybulewicz V, Brown GD, Ruland J (2007) Syk-and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol 8:630–638
Leteux C, Chai W, Loveless RW, Yuen CT, Uhlin-Hansen L, Combarnous Y, Jankovic M, Maric SC, Misulovin Z, Nussenzweig MC, Feizi T (2000) The cysteine-rich domain of the macrophage mannose receptor is a multispecific lectin that recognizes chondroitin sulfates a and B and sulfated oligosaccharides of blood group Lewis(a) and Lewis(x) types in addition to the sulfated N-glycans of lutropin. J Exp Med 191:1117–1126
Li J, Pei H, Zhu B, Liang L, Wei M, He Y, Chen N, Li D, Huang Q, Fan C (2011) Self-assembled multivalent DNA nanostructures for noninvasive intracellular delivery of immunostimulatory CpG oligonucleotides. ACS Nano 5:8783–8789
Li J, Song W, Czerwinski DK, Varghese B, Uematsu S, Akira S, Krieg AM, Levy R (2007) Lymphoma immunotherapy with CpG oligodeoxynucleotides requires TLR9 either in the host or in the tumor itself. J Immunol 179:2493–2500
Li L, Yin Q, Kuss P, Maliga Z, Millán JL, Wu H, Mitchison TJ (2014) Hydrolysis of 2’3’-cGAMP by ENPP1 and design of nonhydrolyzable analogs. Nat Chem Biol 10:1043–1048
Li S, Liang X, Ma L, Shen L, Li T, Zheng L, Sun A, Shang W, Chen C, Zhao W (2018) MiR-22 sustains NLRP3 expression and attenuates H. pylori-induced gastric carcinogenesis. Oncogene 37:884–896
Li S, Luo M, Wang Z, Feng Q, Wilhelm J, Wang X, Li W, Wang J, Cholka A, Fu Y-X, Sumer BD, Yu H, Gao J (2021) Prolonged activation of innate immune pathways by a polyvalent STING agonist. Nat Biomedical Eng 5:455–466
Li T, Hua C, Yue W, Wu J, Lv X, Wei Q, Zhu S, Zang G, Cui J, Liu YJ, Chen J (2020) Discrepant antitumor efficacies of three CpG oligodeoxynucleotide classes in monotherapy and co-therapy with PD-1 blockade. Pharmacol Res 161:105293
Lin LL, Huang CC, Wu MT, Hsu WM, Chuang JH (2018) Innate immune sensor laboratory of genetics and physiology 2 suppresses tumor cell growth and functions as a prognostic marker in neuroblastoma. Cancer Sci 109:3494–3502
Liu X, Pu Y, Cron K, Deng L, Kline J, Frazier WA, Xu H, Peng H, Fu YX, Xu MM (2015) CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. Nat Med 21:1209–1215
Liu Y, Yin Y, Wang L, Zhang W, Chen X, Yang X, Xu J, Ma G (2013) Surface hydrophobicity of microparticles modulates adjuvanticity. J Mater Chem B 1:3888–3896
Llorente A, Skotland T, Sylvänne T, Kauhanen D, Róg T, Orłowski A, Vattulainen I, Ekroos K, Sandvig K (2013) Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim Biophys Acta 1831:1302–1309
Lobato-Pascual A, Saether PC, Fossum S, Dissen E, Daws MR (2013) Mincle, the receptor for mycobacterial cord factor, forms a functional receptor complex with MCL and FcεRI-γ. Eur J Immunol 43:3167–3174
Loetscher M, Gerber B, Loetscher P, Jones SA, Piali L, Clark-Lewis I, Baggiolini M, Moser B (1996) Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes. J Exp Med 184:963–969
Loetscher M, Loetscher P, Brass N, Meese E, Moser B (1998) Lymphocyte-specific chemokine receptor CXCR3: regulation, chemokine binding and gene localization. Eur J Immunol 28:3696–3705
Lohcharoenkal W, Wang L, Chen YC, Rojanasakul Y (2014) Protein nanoparticles as drug delivery carriers for cancer therapy. Biomed Res Int 2014:180549
Lollo G, Vincent M, Ullio-Gamboa G, Lemaire L, Franconi F, Couez D, Benoit JP (2015) Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma. Int J Pharm 495:972–980
Loo Y-M, Gale M Jr (2011) Immune signaling by RIG-I-like receptors. Immunity 34:680–692
Love KT, Mahon KP, Levins CG, Whitehead KA, Querbes W, Dorkin JR, Qin J, Cantley W, Qin LL, Racie T, Frank-Kamenetsky M, Yip KN, Alvarez R, Sah DW, De Fougerolles A, Fitzgerald K, Koteliansky V, Akinc A, Langer R, Anderson DG (2010) Lipid-like materials for low-dose, in vivo gene silencing. Proc Natl Acad Sci USA 107:1864–1869
Luo M, Wang H, Wang Z, Cai H, Lu Z, Li Y, Du M, Huang G, Wang C, Chen X, Porembka MR, Lea J, Frankel AE, Fu YX, Chen ZJ, Gao J (2017) A STING-activating nanovaccine for cancer immunotherapy. Nat Nanotechnol 12:648–654
Luo X, Lian Q, Li W, Chen L, Zhang R, Yang D, Gao L, Qi X, Liu Z, Liao G (2021) Fully synthetic mincle-dependent self-adjuvanting cancer vaccines elicit robust humoral and T cell-dependent immune responses and protect mice from tumor development. Chem Sci 12:15998–16013
Luo Z, Wang C, Yi H, Li P, Pan H, Liu L, Cai L, Ma Y (2015) Nanovaccine loaded with poly I:C and STAT3 siRNA robustly elicits anti-tumor immune responses through modulating tumor-associated dendritic cells in vivo. Biomaterials 38:50–60
Luster AD, Ravetch JV (1987) Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med 166:1084–1097
Lynn GM, Laga R, Darrah PA, Ishizuka AS, Balaci AJ, Dulcey AE, Pechar M, Pola R, Gerner MY, Yamamoto A, Buechler CR, Quinn KM, Smelkinson MG, Vanek O, Cawood R, Hills T, Vasalatiy O, Kastenmüller K, Francica JR, Stutts L, Tom JK, Ryu KA, Esser-Kahn AP, Etrych T, Fisher KD, Seymour LW, Seder RA (2015) In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity. Nat Biotechnol 33:1201–1210
Man SM, Karki R, Kanneganti TD (2016) AIM2 inflammasome in infection, cancer, and autoimmunity: role in DNA sensing, inflammation, and innate immunity. Eur J Immunol 46:269–280
Mannhalter JW, Neychev HO, Zlabinger GJ, Ahmad R, Eibl MM (1985) Modulation of the human immune response by the non-toxic and non-pyrogenic adjuvant aluminium hydroxide: effect on antigen uptake and antigen presentation. Clin Exp Immunol 61:143–151
Manolova V, Flace A, Bauer M, Schwarz K, Saudan P, Bachmann MF (2008) Nanoparticles target distinct dendritic cell populations according to their size. Eur J Immunol 38:1404–1413
Marabelle A, Kohrt H, Caux C, Levy R (2014) Intratumoral immunization: a new paradigm for cancer therapy. Clin Cancer Res 20:1747–1756
Marshall JD, Fearon K, Abbate C, Subramanian S, Yee P, Gregorio J, Coffman RL, Van Nest G (2003) Identification of a novel CpG DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions. J Leukoc Biol 73:781–792
Mathur R, Zeng W, Hayden MS, Ghosh S (2016) Mice lacking TLR11 exhibit variable Salmonella typhi susceptibility. Cell 164:829–830
Mayor S, Pagano RE (2007) Pathways of clathrin-independent endocytosis. Nat Rev Mol Cell Biol 8:603–612
Meng Z, Lu M (2017) RNA Interference-Induced Innate immunity, off-target effect, or Immune. Adjuvant? Front Immunol 8:331
Meraz IM, Savage DJ, Segura-Ibarra V, Li J, Rhudy J, Gu J, Serda RE (2014) Adjuvant cationic liposomes presenting MPL and IL-12 induce cell death, suppress tumor growth, and alter the cellular phenotype of tumors in a murine model of breast cancer. Mol Pharm 11:3484–3491
Molino NM, Anderson AK, Nelson EL, Wang SW (2013) Biomimetic protein nanoparticles facilitate enhanced dendritic cell activation and cross-presentation. ACS Nano 7:9743–9752
Moore E, Clavijo PE, Davis R, Cash H, Van Waes C, Kim Y, Allen C (2016) Established T cell–inflamed tumors rejected after adaptive resistance was reversed by combination STING activation and PD-1 pathway BlockadeRejection of established tumors with CDN and PD-L1 mAb. Cancer Immunol Res 4:1061–1071
Moreira LO, Zamboni DS (2012) NOD1 and NOD2 signaling in infection and inflammation. Front Immunol 3:328
Morelli AE, Larregina AT, Shufesky WJ, Sullivan ML, Stolz DB, Papworth GD, Zahorchak AF, Logar AJ, Wang Z, Watkins SC, Falo LD Jr, Thomson AW (2004) Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 104:3257–3266
Morishita M, Takahashi Y, Matsumoto A, Nishikawa M, Takakura Y (2016) Exosome-based tumor antigens-adjuvant co-delivery utilizing genetically engineered tumor cell-derived exosomes with immunostimulatory CpG DNA. Biomaterials 111:55–65
Mou Y, Xing Y, Ren H, Cui Z, Zhang Y, Yu G, Urba WJ, Hu Q, Hu H (2017) The Effect of Superparamagnetic Iron Oxide Nanoparticle Surface Charge on Antigen Cross-Presentation. Nanoscale Res Lett 12:52
Moyano DF, Saha K, Prakash G, Yan B, Kong H, Yazdani M, Rotello VM (2014) Fabrication of corona-free nanoparticles with tunable hydrophobicity. ACS Nano 8:6748–6755
Moyano DF, Liu Y, Peer D, Rotello VM (2016) Modulation of Immune Response using Engineered Nanoparticle Surfaces. Small 12:76–82
Moyer TJ, Kato Y, Abraham W, Chang JYH, Kulp DW, Watson N, Turner HL, Menis S, Abbott RK, Bhiman JN, Melo MB, Simon HA, Herrera-De La Mata S, Liang S, Seumois G, Agarwal Y, Li N, Burton DR, Ward AB, Schief WR, Crotty S, Irvine DJ (2020) Engineered immunogen binding to alum adjuvant enhances humoral immunity. Nat Med 26:430–440
Murugaiah V, Tsolaki AG, Kishore U (2020) Collectins: Innate Immune Pattern Recognition Molecules. Adv Exp Med Biol 1204:75–127
Nam J, Son S, Moon JJ (2017) Adjuvant-loaded Spiky Gold nanoparticles for activation of Innate Immune cells. Cell Mol Bioeng 10:341–355
Napoletano C, Rughetti A, Agervig Tarp MP, Coleman J, Bennett EP, Picco G, Sale P, Denda-Nagai K, Irimura T, Mandel U, Clausen H, Frati L, Taylor-Papadimitriou J, Burchell J, Nuti M (2007) Tumor-associated Tn-MUC1 glycoform is internalized through the macrophage galactose-type C-type lectin and delivered to the HLA class I and II compartments in dendritic cells. Cancer Res 67:8358–8367
Naseri N, Valizadeh H, Zakeri-Milani P (2015) Solid lipid nanoparticles and nanostructured lipid carriers: structure, Preparation and Application. Adv Pharm Bull 5:305–313
Nath A, Pal R, Singh LM, Saikia H, Rahaman H, Ghosh SK, Mazumder R, Sengupta M (2018) Gold–manganese oxide nanocomposite suppresses hypoxia and augments pro-inflammatory cytokines in tumor associated macrophages. Int Immunopharmacol 57:157–164
Nguyen TL, Choi Y, Kim J (2019) Mesoporous silica as a versatile platform for Cancer Immunotherapy. Advanced materials (Deerfield Beach. Fla) 31:e1803953
Nguyen TL, Cha BG, Choi Y, Im J, Kim J (2020) Injectable dual-scale mesoporous silica cancer vaccine enabling efficient delivery of antigen/adjuvant-loaded nanoparticles to dendritic cells recruited in local macroporous scaffold. Biomaterials 239:119859
Ni Q, Zhang F, Liu Y, Wang Z, Yu G, Liang B, Niu G, Su T, Zhu G, Lu G, Zhang L, Chen X (2020) A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer. Sci Adv 6:eaaw6071
Norell H, Martins Da Palma T, Lesher A, Kaur N, Mehrotra M, Naga OS, Spivey N, Olafimihan S, Chakraborty NG, Voelkel-Johnson C, Nishimura MI, Mukherji B, Mehrotra S (2009) Inhibition of superoxide generation upon T-cell receptor engagement rescues Mart-1(27–35)-reactive T cells from activation-induced cell death. Cancer Res 69:6282–6289
Nuhn L, Van Hoecke L, Deswarte K, Schepens B, Li Y, Lambrecht BN, De Koker S, David SA, Saelens X, De Geest BG (2018) Potent anti-viral vaccine adjuvant based on pH-degradable nanogels with covalently linked small molecule imidazoquinoline TLR7/8 agonist. Biomaterials 178:643–651
Oberli MA, Reichmuth AM, Dorkin JR, Mitchell MJ, Fenton OS, Jaklenec A, Anderson DG, Langer R, Blankschtein D (2017) Lipid nanoparticle assisted mRNA delivery for Potent Cancer Immunotherapy. Nano Lett 17:1326–1335
Ochyl LJ, Moon JJ (2019) Dendritic cell membrane vesicles for activation and maintenance of Antigen-Specific T cells. Adv Healthc Mater 8:e1801091
Ogawa C, Liu YJ, Kobayashi KS (2011) Muramyl dipeptide and its derivatives: peptide adjuvant in immunological disorders and cancer therapy. Curr Bioact Compd 7:180–197
Oh N, Park JH (2014) Endocytosis and exocytosis of nanoparticles in mammalian cells. Int J Nanomed 9(Suppl 1):51–63
Oliveira-Nascimento L, Massari P, Wetzler LM (2012) The role of TLR2 in infection and immunity. Front Immunol 3:79
O’neill LA, Bryant CE, Doyle SL (2009) Therapeutic targeting of toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev 61:177–197
Ostrop J, Jozefowski K, Zimmermann S, Hofmann K, Strasser E, Lepenies B, Lang R (2015) Contribution of MINCLE-SYK Signaling to Activation of Primary Human APCs by Mycobacterial Cord Factor and the Novel Adjuvant TDB. Journal of immunology (Baltimore, Md.: 1950) 195:2417–2428
Palti Y (2011) Toll-like receptors in bony fish: from genomics to function. Dev Comp Immunol 35:1263–1272
Pandey S, Singh S, Anang V, Bhatt AN, Natarajan K, Dwarakanath BS (2015) Pattern Recognition Receptors in Cancer Progression and Metastasis. Cancer Growth and Metastasis 8:25–34
Park JH, Kim YG, Mcdonald C, Kanneganti TD, Hasegawa M, Body-Malapel M, Inohara N, Núñez G (2007) RICK/RIP2 mediates innate immune responses induced through Nod1 and Nod2 but not TLRs. Journal of immunology (Baltimore, Md.: 1950) 178:2380–2386
Parodi A, Quattrocchi N, Van De Ven AL, Chiappini C, Evangelopoulos M, Martinez JO, Brown BS, Khaled SZ, Yazdi IK, Enzo MV, Isenhart L, Ferrari M, Tasciotti E (2013) Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nat Nanotechnol 8:61–68
Patel JM, Vartabedian VF, Bozeman EN, Caoyonan BE, Srivatsan S, Pack CD, Dey P, D’souza MJ, Yang L, Selvaraj P (2016) Plasma membrane vesicles decorated with glycolipid-anchored antigens and adjuvants via protein transfer as an antigen delivery platform for inhibition of tumor growth. Biomaterials 74:231–244
Patel SA, Minn AJ (2018) Combination Cancer Therapy with Immune Checkpoint Blockade: mechanisms and strategies. Immunity 48:417–433
Patin EC, Willcocks S, Orr S, Ward TH, Lang R, Schaible UE (2016) Mincle-mediated anti-inflammatory IL-10 response counter-regulates IL-12 in vitro. Innate Immun 22:181–185
Peek LJ, Middaugh CR, Berkland C (2008) Nanotechnology in vaccine delivery. Adv Drug Deliv Rev 60:915–928
Pelka K, Latz E (2011) Getting closer to the dirty little secret. Immunity 34:455–458
Peng S, Cao F, Xia Y, Gao XD, Dai L, Yan J, Ma G (2020) Particulate Alum via Pickering Emulsion for an Enhanced COVID-19 Vaccine Adjuvant. Advanced materials (Deerfield Beach, Fla.) 32:e2004210
Petersen LK, Ramer-Tait AE, Broderick SR, Kong CS, Ulery BD, Rajan K, Wannemuehler MJ, Narasimhan B (2011) Activation of innate immune responses in a pathogen-mimicking manner by amphiphilic polyanhydride nanoparticle adjuvants. Biomaterials 32:6815–6822
Petrarca C, Clemente E, Amato V, Pedata P, Sabbioni E, Bernardini G, Iavicoli I, Cortese S, Niu Q, Otsuki T, Paganelli R, Di Gioacchino M (2015) Engineered metal based nanoparticles and innate immunity. Clin Mol Allergy: CMA 13:13
Pitt JM, Charrier M, Viaud S, André F, Besse B, Chaput N, Zitvogel L (2014) Dendritic cell-derived exosomes as immunotherapies in the fight against cancer. Journal of immunology (Baltimore, Md.: 1950) 193:1006–1011
Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene, vol 282. Science, New York, N.Y.), pp 2085–2088
Pradere J-P, Dapito DH, Schwabe RF (2014) The Yin and Yang of toll-like receptors in cancer. Oncogene 33:3485–3495
Pricop D, Andrieş M (2014) Endocytosis and exocytosis of gold nanoparticles. Int J Nano 25:1–9
Quinn KM, Yamamoto A, Costa A, Darrah PA, Lindsay RW, Hegde ST, Johnson TR, Flynn BJ, Loré K, Seder RA (2013) Coadministration of polyinosinic:polycytidylic acid and immunostimulatory complexes modifies antigen processing in dendritic cell subsets and enhances HIV gag-specific T cell immunity. Journal of immunology (Baltimore, Md.: 1950) 191:5085–5096
Rimaniol AC, Gras G, Verdier F, Capel F, Grigoriev VB, Porcheray F, Sauzeat E, Fournier JG, Clayette P, Siegrist CA, Dormont D (2004) Aluminum hydroxide adjuvant induces macrophage differentiation towards a specialized antigen-presenting cell type. Vaccine 22:3127–3135
Robinson MJ, Osorio F, Rosas M, Freitas RP, Schweighoffer E, Gross O, Verbeek JS, Ruland J, Tybulewicz V, Brown GD, Moita LF, Taylor PR, Reis E, Sousa C (2009) Dectin-2 is a syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. J Exp Med 206:2037–2051
Röck J, Schneider E, Grün JR, Grützkau A, Küppers R, Schmitz J, Winkels G (2007) CD303 (BDCA-2) signals in plasmacytoid dendritic cells via a BCR‐like signalosome involving Syk, Slp65 and PLCγ2. Eur J Immunol 37:3564–3575
Roeder A, Kirschning CJ, Rupec RA, Schaller M, Weindl G, Korting HC (2004) Toll-like receptors as key mediators in innate antifungal immunity. Med Mycol 42:485–498
Rotte A (2019) Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J Experimental Clin Cancer Res 38:255
Saha K, Rahimi M, Yazdani M, Kim ST, Moyano DF, Hou S, Das R, Mout R, Rezaee F, Mahmoudi M, Rotello VM (2016) Regulation of Macrophage Recognition through the interplay of Nanoparticle Surface Functionality and Protein Corona. ACS Nano 10:4421–4430
Saikia C, Gogoi PJ, Maji TKJJOM, Medicine G (2015) Chitosan: A Promising Biopolymer in Drug Delivery Applications. 2015:1–10
Salaun B, Coste I, Rissoan MC, Lebecque SJ, Renno T (2006) TLR3 can directly trigger apoptosis in human cancer cells. Journal of immunology (Baltimore, Md.: 1950) 176:4894–4901
Salazar AM, Erlich RB, Mark A, Bhardwaj N, Herberman RB (2014) Therapeutic in situ autovaccination against solid cancers with intratumoral poly-ICLC: case report, hypothesis, and clinical trial. Cancer Immunol Res 2:720–724
Saleh M (2011) The machinery of nod-like receptors: refining the paths to immunity and cell death. Immunol Rev 243:235–246
Sanders H, Feavers IM (2011) Adjuvant properties of meningococcal outer membrane vesicles and the use of adjuvants in Neisseria meningitidis protein vaccines. Expert Rev Vaccines 10:323–334
Sato K, Yang XL, Yudate T, Chung JS, Wu J, Luby-Phelps K, Kimberly RP, Underhill D, Cruz PD Jr, Ariizumi K (2006) Dectin-2 is a pattern recognition receptor for fungi that couples with the fc receptor gamma chain to induce innate immune responses. J Biol Chem 281:38854–38866
Scheffel F, Knuschke T, Otto L, Kollenda S, Sokolova V, Cosmovici C, Buer J, Timm J, Epple M, Westendorf AM (2020) Effective activation of Human Antigen-Presenting cells and cytotoxic CD8(+) T cells by a calcium phosphate-based nanoparticle vaccine delivery system. Vaccines 8.
Schneider C, Schmidt T, Ziske C, Tiemann K, Lee KM, Uhlinsky V, Behrens P, Sauerbruch T, Schmidt-Wolf IG, Mühlradt PF, Schmidt J, Märten A (2004) Tumour suppression induced by the macrophage activating lipopeptide MALP-2 in an ultrasound guided pancreatic carcinoma mouse model. Gut 53:355–361
Schwarz K, Meijerink E, Speiser DE, Tissot AC, Cielens I, Renhof R, Dishlers A, Pumpens P, Bachmann MF (2005) Efficient homologous prime-boost strategies for T cell vaccination based on virus-like particles. Eur J Immunol 35:816–821
Schwarz TF (2009) Clinical update of the AS04-adjuvanted human papillomavirus-16/18 cervical cancer vaccine. Cervarix Adv Therapy 26:983–998
Schwechheimer C, Kuehn MJ (2015) Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions. Nat Rev Microbiol 13:605–619
Seth A, Heo MB, Sung MH, Lim YT (2015) Infection-mimicking poly(γ-glutamic acid) as adjuvant material for effective anti-tumor immune response. Int J Biol Macromol 75:495–504
Shang L, Nienhaus K, Nienhaus GU (2014) Engineered nanoparticles interacting with cells: size matters. J Nanobiotechnol 12:5
Shao K, Singha S, Clemente-Casares X, Tsai S, Yang Y, Santamaria P (2015) Nanoparticle-based immunotherapy for cancer. ACS Nano 9:16–30
Shekarian T, Valsesia-Wittmann S, Brody J, Michallet MC, Depil S, Caux C, Marabelle A (2017) Pattern recognition receptors: immune targets to enhance cancer immunotherapy. Ann Oncol 28:1756–1766
Shetab Boushehri MA, Lamprecht A (2018) TLR4-Based immunotherapeutics in Cancer: a review of the achievements and shortcomings. Mol Pharm 15:4777–4800
Shima F, Akagi T, Akashi M (2015) Effect of hydrophobic side chains in the induction of Immune responses by nanoparticle adjuvants consisting of amphiphilic poly(γ-glutamic acid). Bioconjug Chem 26:890–898
Siefert AL, Caplan MJ, Fahmy TM (2016) Artificial bacterial biomimetic nanoparticles synergize pathogen-associated molecular patterns for vaccine efficacy. Biomaterials 97:85–96
Singh SK, Streng-Ouwehand I, Litjens M, Kalay H, Burgdorf S, Saeland E, Kurts C, Unger WW, Van Kooyk Y (2011) Design of neo-glycoconjugates that target the mannose receptor and enhance TLR-independent cross-presentation and Th1 polarization. Eur J Immunol 41:916–925
Song W, Das M, Xu Y, Si X, Zhang Y, Tang Z, Chen XJMTN (2019) Leveraging biomaterials for cancer immunotherapy: targeting pattern recognition receptors. 5:100029
Storni T, Ruedl C, Schwarz K, Schwendener RA, Renner WA, Bachmann MF (2004) Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. Journal of immunology (Baltimore, Md.: 1950) 172:1777–1785
Sun B, Ji Z, Liao YP, Wang M, Wang X, Dong J, Chang CH, Li R, Zhang H, Nel AE, Xia T (2013a) Engineering an effective immune adjuvant by designed control of shape and crystallinity of aluminum oxyhydroxide nanoparticles. ACS Nano 7:10834–10849
Sun B, Zhao X, Gu W, Cao P, Movahedi F, Wu Y, Xu ZP, Gu W (2021a) ATP stabilised and sensitised calcium phosphate nanoparticles as effective adjuvants for a DNA vaccine against cancer. J Mater Chem B 9:7435–7446
Sun L, Kees T, Almeida AS, Liu B, He XY, Ng D, Han X, Spector DL, Mcneish IA, Gimotty P, Adams S, Egeblad M (2021b) Activating a collaborative innate-adaptive immune response to control metastasis. Cancer Cell 39:1361–1374e1369
Sun L, Wu J, Du F, Chen X, Chen ZJ (2013b) Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science (New York, N.Y.) 339:786–791
Sun X, Zhang Y, Li J, Park KS, Han K, Zhou X, Xu Y, Nam J, Xu J, Shi X, Wei L, Lei YL, Moon JJ (2021c) Amplifying STING activation by cyclic dinucleotide-manganese particles for local and systemic cancer metalloimmunotherapy. Nat Nanotechnol 16:1260–1270
Sun Y, Liu J (2014) Potential of cancer cell-derived exosomes in clinical application: a review of recent research advances. Clin Ther 36:863–872
Sun ZY, Chen PG, Liu YF, Shi L, Zhang BD, Wu JJ, Zhao YF, Chen YX, Li YM (2017) Self-assembled Nano-Immunostimulant for Synergistic Immune activation. Chembiochem: A European Journal of Chemical Biology 18:1721–1729
Sutmuller RP, Den Brok MH, Kramer M, Bennink EJ, Toonen LW, Kullberg B-J, Joosten LA, Akira S, Netea MG, Adema GJ (2006) Toll-like receptor 2 controls expansion and function of regulatory T cells. J Clin Investig 116:485–494
Swanson CL, Wilson TJ, Strauch P, Colonna M, Pelanda R, Torres RM (2010) Type I IFN enhances follicular B cell contribution to the T cell–independent antibody response. J Exp Med 207:1485–1500
Swanson KV, Deng M, Ting JP-Y (2019) The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol 19:477–489
Tada H, Nemoto E, Shimauchi H, Watanabe T, Mikami T, Matsumoto T, Ohno N, Tamura H, Shibata K, Akashi S, Miyake K, Sugawara S, Takada H (2002) Saccharomyces cerevisiae- and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by human monocytes in a CD14- and toll-like receptor 4-dependent manner. Microbiol Immunol 46:503–512
Takahashi H, Misato K, Aoshi T, Yamamoto Y, Kubota Y, Wu X, Kuroda E, Ishii KJ, Yamamoto H, Yoshioka Y (2018) Carbonate apatite Nanoparticles Act as Potent Vaccine Adjuvant Delivery Vehicles by enhancing Cytokine Production Induced by Encapsulated cytosine-phosphate-guanine oligodeoxynucleotides. Front Immunol 9:783
Takeda K, Akira S (2005) Toll-like receptors in innate immunity. Int Immunol 17:1–14
Takeuchi O, Akira S (2010) Pattern recognition receptors and inflammation. Cell 140:805–820
Tel J, Benitez-Ribas D, Hoosemans S, Cambi A, Adema GJ, Figdor CG, Tacken PJ, De Vries IJM (2011) DEC‐205 mediates antigen uptake and presentation by both resting and activated human plasmacytoid dendritic cells. Eur J Immunol 41:1014–1023
Temizoz B, Hioki K, Kobari S, Jounai N, Kusakabe T, Lee MSJ, Coban C, Kuroda E, Ishii KJ (2022) Anti-tumor immunity by transcriptional synergy between TLR9 and STING activation. Int Immunol 34:353–364
Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, Miyake K, Freudenberg M, Galanos C, Simon JC (2002) Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med 195:99–111
Thomas M, Sadjadian P, Kollmeier J, Lowe J, Mattson P, Trout J, Gargano M, Patchen M, Walsh R, Beliveau M (2017) A randomized, open-label, multicenter, phase II study evaluating the efficacy and safety of BTH1677 (1, 3–1, 6 beta glucan; Imprime PGG) in combination with cetuximab and chemotherapy in patients with advanced non-small cell lung cancer. Investig New Drugs 35:345–358
Théry C, Ostrowski M, Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9:581–593
Tomić S, Ðokić J, Vasilijić S, Ogrinc N, Rudolf R, Pelicon P, Vučević D, Milosavljević P, Janković S, Anžel I, Rajković J, Rupnik MS, Friedrich B, Colić M (2014) Size-dependent effects of gold nanoparticles uptake on maturation and antitumor functions of human dendritic cells in vitro. PLoS ONE 9:e96584
Tretiakova DS, Vodovozova EL (2022) Liposomes as Adjuvants and Vaccine Delivery Systems. Biochemistry (Moscow) supplement. Series A. Membrane and cell Biology 16:1–20
Trumpfheller C, Caskey M, Nchinda G, Longhi MP, Mizenina O, Huang Y, Schlesinger SJ, Colonna M, Steinman RM (2008) The microbial mimic poly IC induces durable and protective CD4 + T cell immunity together with a dendritic cell targeted vaccine. Proc Natl Acad Sci USA 105:2574–2579
Uto T, Akagi T, Toyama M, Nishi Y, Shima F, Akashi M, Baba M (2011) Comparative activity of biodegradable nanoparticles with aluminum adjuvants: antigen uptake by dendritic cells and induction of immune response in mice. Immunol Lett 140:36–43
Van Den Boorn JG, Hartmann G (2013) Turning tumors into vaccines: co-opting the innate immune system. Immunity 39:27–37
Vermaelen K (2019) Vaccine strategies to Improve Anti-cancer Cellular Immune responses. Front Immunol 10:8
Vijayan D, Young A, Teng MWL, Smyth MJ (2017) Targeting immunosuppressive adenosine in cancer. Nat Rev Cancer 17:709–724
Vivier E, Malissen B (2005) Innate and adaptive immunity: specificities and signaling hierarchies revisited. Nat Immunol 6:17–21
Vollmer J, Weeratna R, Payette P, Jurk M, Schetter C, Laucht M, Wader T, Tluk S, Liu M, Davis HL, Krieg AM (2004) Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities. Eur J Immunol 34:251–262
Walkey CD, Olsen JB, Guo H, Emili A, Chan WC (2012) Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J Am Chem Soc 134:2139–2147
Wang C, Sun W, Wright G, Wang AZ, Gu Z (2016) Inflammation-triggered Cancer immunotherapy by programmed delivery of CpG and Anti-PD1 antibody. Advanced materials (Deerfield Beach. Fla) 28:8912–8920
Wang C, Guan Y, Lv M, Zhang R, Guo Z, Wei X, Du X, Yang J, Li T, Wan Y, Su X, Huang X, Jiang Z (2018) Manganese increases the sensitivity of the cGAS-STING pathway for double-stranded DNA and is required for the host defense against DNA viruses. Immunity 48:675–687e677
Wang D, Guo Z, Ma X, Hu Y, Huang X, Fan Y, Yang S, Guo LJCP (2010) Effects of sulfated lentinan on cellular infectivity of avian infectious bronchitis virus. 79:461–465
Wang F, Zhang R, Wu Q, Chen T, Sun P, Shi AC (2014) Probing the nanostructure, interfacial interaction, and dynamics of chitosan-based nanoparticles by multiscale solid-state NMR. ACS Appl Mater Interfaces 6:21397–21407
Wang L, Liu Y, Li W, Jiang X, Ji Y, Wu X, Xu L, Qiu Y, Zhao K, Wei T (2011) Selective targeting of gold nanorods at the mitochondria of cancer cells: implications for cancer therapy. Nano Lett 11:772–780
Wang L, He Y, He T, Liu G, Lin C, Li K, Lu L, Cai K (2020) Lymph node-targeted immune-activation mediated by imiquimod-loaded mesoporous polydopamine based-nanocarriers. Biomaterials 255:120208
Watson A, Madsen J, Clark HW (2020) SP-A and SP-D: dual functioning Immune Molecules with Antiviral and Immunomodulatory Properties. Front Immunol 11:622598
Weis WI, Drickamer K, Hendrickson WA (1992) Structure of a C-type mannose-binding protein complexed with an oligosaccharide. Nature 360:127–134
Williamson JR, Raghuraman MK, Cech TR (1989) Monovalent cation-induced structure of telomeric DNA: the G-quartet model. Cell 59:871–880
Wilson DS, Hirosue S, Raczy MM, Bonilla-Ramirez L, Jeanbart L, Wang R, Kwissa M, Franetich JF, Broggi MaS, Diaceri G, Quaglia-Thermes X, Mazier D, Swartz MA, Hubbell JA (2019) Antigens reversibly conjugated to a polymeric glyco-adjuvant induce protective humoral and cellular immunity. Nat Mater 18:175–185
Woo S-R, Fuertes MB, Corrales L, Spranger S, Furdyna MJ, Leung MY, Duggan R, Wang Y, Barber GN, Fitzgerald KA (2014) STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity 41:830–842
Wu X, Yamamoto H, Nakanishi H, Yamamoto Y, Inoue A, Tei M, Hirose H, Uemura M, Nishimura J, Hata T, Takemasa I, Mizushima T, Hossain S, Akaike T, Matsuura N, Doki Y, Mori M (2015) Innovative delivery of siRNA to solid tumors by super carbonate apatite. PLoS ONE 10:e0116022
Xia Q, Gong C, Gu F, Wang Z, Hu C, Zhang L, Qiang L, Ding X, Gao S, Gao Y (2018) Functionalized Multi-Walled Carbon Nanotubes for Targeting Delivery of Immunostimulatory CpG oligonucleotides against prostate Cancer. J Biomed Nanotechnol 14:1613–1626
Xing J, Liu Z, Huang Y, Qin T, Bo R, Zheng S, Luo L, Huang Y, Niu Y, Wang D (2016) Lentinan-Modified Carbon Nanotubes as an Antigen Delivery System modulate Immune Response in Vitro and in vivo. ACS Appl Mater Interfaces 8:19276–19283
Xiong Z, Ohlfest JR (2011) Topical imiquimod has therapeutic and immunomodulatory effects against intracranial tumors. Journal of immunotherapy (Hagerstown, Md.: 1997) 34:264–269
Xu Y, Sherwood JA, Lackey KH, Qin Y, Bao Y (2016) The responses of immune cells to iron oxide nanoparticles. J Appl Toxicology: JAT 36:543–553
Xu Y, Ma S, Zhao J, Chen H, Si X, Huang Z, Yu Z, Song W, Tang Z, Chen X (2022) Mannan-decorated pathogen-like polymeric nanoparticles as nanovaccine carriers for eliciting superior anticancer immunity. Biomaterials 284:121489
Yamamoto H, Oda M, Nakano M, Watanabe N, Yabiku K, Shibutani M, Inoue M, Imagawa H, Nagahama M, Himeno S, Setsu K, Sakurai J, Nishizawa M (2013) Development of vizantin, a safe immunostimulant, based on the structure-activity relationship of trehalose-6,6’-dicorynomycolate. J Med Chem 56:381–385
Yamasaki S, Ishikawa E, Sakuma M, Hara H, Ogata K, Saito T (2008) Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nat Immunol 9:1179–1188
Yamasaki S, Matsumoto M, Takeuchi O, Matsuzawa T, Ishikawa E, Sakuma M, Tateno H, Uno J, Hirabayashi J, Mikami Y, Takeda K, Akira S, Saito T (2009) C-type lectin mincle is an activating receptor for pathogenic fungus. Malassezia Proc Natl Acad Sci United States Am 106:1897–1902
Yan D, Wei YQ, Guo HC, Sun SQ (2015b) The application of virus-like particles as vaccines and biological vehicles. Appl Microbiol Biotechnol 99:10415–10432
Yan H, Kamiya T, Suabjakyong P, Tsuji NM (2015a) Targeting C-type lectin receptors for cancer immunity. Front Immunol 6:408
Yang R, Xu J, Xu L, Sun X, Chen Q, Zhao Y, Peng R, Liu Z (2018) Cancer Cell membrane-coated adjuvant nanoparticles with mannose modification for effective anticancer vaccination. ACS Nano 12:5121–5129
Yang Y, Jambhrunkar M, Abbaraju PL, Yu M, Zhang M, Yu C (2017) Understanding the Effect of Surface Chemistry of Mesoporous Silica Nanorods on Their Vaccine Adjuvant Potency. Advanced healthcare materials 6
Yildiz S, Alpdundar E, Gungor B, Kahraman T, Bayyurt B, Gursel I, Gursel M (2015) Enhanced immunostimulatory activity of cyclic dinucleotides on mouse cells when complexed with a cell-penetrating peptide or combined with CpG. Eur J Immunol 45:1170–1179
Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S, Fujita T (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 5:730–737
Yoshino S, Tabata T, Hazama S, Iizuka N, Yamamoto K, Hirayama M, Tangoku A, Oka M (2000) Immunoregulatory effects of the antitumor polysaccharide lentinan on Th1/Th2 balance in patients with digestive cancers. Anticancer Res 20:4707–4711
Zaharoff DA, Rogers CJ, Hance KW, Schlom J, Greiner JW (2007) Chitosan solution enhances both humoral and cell-mediated immune responses to subcutaneous vaccination. Vaccine 25:2085–2094
Zaidi AH, Kelly RJ, Gorbunova A, Omstead AN, Salvitti MS, Zheng P, Kosovec JE, Lee S, Ayazi S, Babar L, Finley GG, Goel A, Jobe BA (2021) Intratumoral immunotherapy with STING agonist, ADU-S100, induces CD8 + T-cell mediated anti-tumor immunity in an esophageal adenocarcinoma model. Oncotarget 12:292–303
Zariri A, Beskers J, Van De Waterbeemd B, Hamstra HJ, Bindels TH, Van Riet E, Van Putten JP, Van Der Ley P (2016) Meningococcal outer membrane vesicle composition-dependent activation of the Innate Immune Response. Infect Immun 84:3024–3033
Żelechowska P, Brzezińska-Błaszczyk E, Różalska S, Agier J, Kozłowska E (2021) Mannan activates tissue native and IgE-sensitized mast cells to proinflammatory response and chemotaxis in TLR4-dependent manner. J Leukoc Biol 109:931–942
Zhang B-D, Wu J-J, Li W-H, Hu H-G, Zhao L, He P-Y, Zhao Y-F, Li Y-M (2022b) STING and TLR7/8 agonists-based nanovaccines for synergistic antitumor immune activation. Nano Res 15:6328–6339
Zhang J-G, Czabotar PE, Policheni AN, Caminschi I, San Wan S, Kitsoulis S, Tullett KM, Robin AY, Brammananth R, Van Delft MF (2012) The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments. Immunity 36:646–657
Zhang L, Zhu G, Mei L, Wu C, Qiu L, Cui C, Liu Y, Teng IT, Tan W (2015) Self-assembled DNA immunonanoflowers as multivalent CpG nanoagents. ACS Appl Mater Interfaces 7:24069–24074
Zhang R, Wang C, Guan Y, Wei X, Sha M, Yi M, Jing M, Lv M, Guo W, Xu J, Wan Y, Jia XM, Jiang Z (2021) Manganese salts function as potent adjuvants. Cell Mol Immunol 18:1222–1234
Zhang S, Liu Y, Zhou J, Wang J, Jin G, Wang X (2022a) Breast Cancer Vaccine containing a Novel toll-like receptor 7 agonist and an aluminum adjuvant exerts Antitumor Effects. International journal of molecular sciences 23.
Zhang W, An M, Xi J, Liu H (2017) Targeting CpG adjuvant to Lymph Node via Dextran Conjugate enhances Antitumor Immunotherapy. Bioconjug Chem 28:1993–2000
Zhang Y, Sun Z, Pei J, Luo Q, Zeng X, Li Q, Yang Z, Quan J (2018) Identification of α-Mangostin as an agonist of human STING. ChemMedChem 13:2057–2064
Zhan Z, Xie X, Cao H, Zhou X, Zhang XD, Fan H, Liu Z (2014) Autophagy facilitates TLR4- and TLR3-triggered migration and invasion of lung cancer cells through the promotion of TRAF6 ubiquitination. Autophagy 10:257–268
Zhao F, Guo Z, Ma Z-R, Ma L-L, Zhao J (2021) Antitumor activities of Grifola frondosa (maitake) polysaccharide: a meta-analysis based on preclinical evidence and quality assessment. J Ethnopharmacol 280:114395
Zhao Z, Ma Z, Wang B, Guan Y, Su XD, Jiang Z (2020) Mn(2+) directly activates cGAS and structural analysis suggests Mn(2+) induces a noncanonical Catalytic synthesis of 2’3’-cGAMP. Cell Rep 32:108053
Zitvogel L, Galluzzi L, Kepp O, Smyth MJ, Kroemer G (2015) Type I interferons in anticancer immunity. Nat Rev Immunol 15:405–414
Zom GG, Willems M, Meeuwenoord NJ, Reintjens NRM, Tondini E, Khan S, Overkleeft HS, Van Der Marel GA, Codee JDC, Ossendorp F, Filippov DV (2019) Dual synthetic peptide Conjugate Vaccine simultaneously triggers TLR2 and NOD2 and activates human dendritic cells. Bioconjug Chem 30:1150–1161
Acknowledgements
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2022R1A2C1006643, 2022R1A4A3026347). All figures were created with Biorender.com.
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Li, Z., Rana, I., Park, G. et al. Pattern recognition receptors and their nano-adjuvants for cancer immunotherapy. J. Pharm. Investig. 53, 685–706 (2023). https://doi.org/10.1007/s40005-023-00633-y
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DOI: https://doi.org/10.1007/s40005-023-00633-y