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Oxidative Stress in the Tumor Immune Microenvironment

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Oxidative Stress

Abstract

Oxidative stress is one of defining features of the tumor microenvironment, which is closely related to the interactions between tumor cells and stromal cells. It affects tumor progression in many aspects. In the tumor microenvironment, primary immune cells have different functions, which together make up the immune defense line of the tumor. This review focuses on the relationship between oxidative stress and tumor-related immune system, specifically the effects and mechanisms of oxidative stress on different cell processes of immune cells in the tumor microenvironment. Then, we discuss the main overall effect of oxidative stress, immunosuppression, and its inspiration for tumor immunotherapy, which provides a theoretical basis for the feasibility of oxidative stress as a new target of tumor immunotherapy.

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References

  1. Fiaschi T, Chiarugi P. Oxidative stress, tumor microenvironment, and metabolic reprogramming: a diabolic liaison. Int J Cell Biol. 2012;2012:762825. https://doi.org/10.1155/2012/762825.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bhattacharyya S. Tumour, oxidative stress and host T cell response: cementing the dominance. Scand J Immunol. 2015;6:82.

    Google Scholar 

  3. Whiteside TL. Immune suppression in cancer: effects on immune cells, mechanisms and future therapeutic intervention. Semin Cancer Biol. 2006;16(1):3–15. https://doi.org/10.1016/j.semcancer.2005.07.008.

    Article  CAS  PubMed  Google Scholar 

  4. Cheng YT, Yang CC, Shyur LF. Phytomedicine-modulating oxidative stress and the tumor microenvironment for cancer therapy. Pharmacol Res. 2016;114:128–43. https://doi.org/10.1016/j.phrs.2016.10.022.

    Article  CAS  PubMed  Google Scholar 

  5. Steinman RM. Decisions about dendritic cells: past, present, and future. Annu Rev Immunol. 2012;30:1–22. https://doi.org/10.1146/annurev-immunol-100311-102839.

    Article  CAS  PubMed  Google Scholar 

  6. Liu YJ. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol. 2005;23:275–306. https://doi.org/10.1146/annurev.immunol.23.021704.115633.

    Article  CAS  PubMed  Google Scholar 

  7. Binnewies M, Mujal AM, Pollack JL, Combes AJ, Hardison EA, Barry KC, Tsui J, Ruhland MK, Kersten K, Abushawish MA, Spasic M, Giurintano JP, Chan V, Daud AI, Ha P, Ye CJ, Roberts EW, Krummel MF. Unleashing type-2 dendritic cells to drive protective antitumor CD4(+) T cell immunity. Cell. 2019;177(3):556–71. https://doi.org/10.1016/j.cell.2019.02.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL, Erle DJ, Barczak A, Rosenblum MD, Daud A, Barber DL, Amigorena S, Veer LJ, Sperling AI, Wolf DM, Krummel MF. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell. 2014;26(5):638–52. https://doi.org/10.1016/j.ccell.2014.09.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Woo SR, Fuertes MB, Corrales L, Spranger S, Furdyna MJ, Leung MY, Duggan R, Wang Y, Barber GN, Fitzgerald KA, Alegre ML, Gajewski TF. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity. 2014;41(5):830–42. https://doi.org/10.1016/j.immuni.2014.10.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dustin ML, Bromley SK, Kan Z, Peterson DA, Unanue ER. Antigen receptor engagement delivers a stop signal to migrating T lymphocytes. Proc Natl Acad Sci U S A. 1997;94(8):3909–13. https://doi.org/10.1073/pnas.94.8.3909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Stinchcombe JC, Bossi G, Booth S, Griffiths GM. The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity. 2001;15(5):751–61. https://doi.org/10.1016/s1074-7613(01)00234-5.

    Article  CAS  PubMed  Google Scholar 

  12. Boissonnas A, Fetler L, Zeelenberg IS, Hugues S, Amigorena S. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor. J Exp Med. 2007;204(2):345–56. https://doi.org/10.1084/jem.20061890.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Breart B, Lemaitre F, Celli S, Bousso P. Two-photon imaging of intratumoral CD8+ T cell cytotoxic activity during adoptive T cell therapy in mice. J Clin Invest. 2008;118(4):1390–7. https://doi.org/10.1172/JCI34388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Feig C, Jones JO, Kraman M, Wells RJB, Deonarine A, Chan DS, Connell CM, Roberts EW, Zhao Q, Caballero OL, Teichmann SA, Janowitz T, Jodrell DI, Tuveson DA, Fearon DT. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci U S A. 2013;110(50):20212–7. https://doi.org/10.1073/pnas.1320318110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Markiewicz MA, Wise EL, Buchwald ZS, Cheney EE, Hansen TH, Suri A, Cemerski S, Allen PM, Shaw AS. IL-12 enhances CTL synapse formation and induces self-reactivity. J Immunol. 2009;182(3):1351–61. https://doi.org/10.4049/jimmunol.182.3.1351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Melssen M, Slingluff CL Jr. Vaccines targeting helper T cells for cancer immunotherapy. Curr Opin Immunol. 2017;47:85–92. https://doi.org/10.1016/j.coi.2017.07.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kennedy R, Celis E. Multiple roles for CD4+ T cells in anti-tumor immune responses. Immunol Rev. 2008;222:129–44. https://doi.org/10.1111/j.1600-065X.2008.00616.x.

    Article  CAS  PubMed  Google Scholar 

  18. Tateyama M, Oyaizu N, McCloskey TW, Than S, Pahwa S. CD4 T lymphocytes are primed to express Fas ligand by CD4 cross-linking and to contribute to CD8 T-cell apoptosis via Fas/FasL death signaling pathway. Blood. 2000;96(1):195–202.

    Article  CAS  Google Scholar 

  19. Kumar P, Bhattacharya P, Prabhakar BS. A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity. J Autoimmun. 2018;95:77–99. https://doi.org/10.1016/j.jaut.2018.08.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 2006;6(4):295–307. https://doi.org/10.1038/nri1806.

    Article  CAS  PubMed  Google Scholar 

  21. Grossman WJ, Verbsky JW, Barchet W, Colonna M, Atkinson JP, Ley TJ. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity. 2004;21(4):589–601. https://doi.org/10.1016/j.immuni.2004.09.002.

    Article  CAS  PubMed  Google Scholar 

  22. Sarhan D, Hippen KL, Lemire A, Hying S, Luo X, Lenvik T, Curtsinger J, Davis Z, Zhang B, Cooley S, Cichocki F, Blazar BR, Miller JS. Adaptive NK cells resist regulatory T-cell suppression driven by IL37. Cancer Immunol Res. 2018;6(7):766–75. https://doi.org/10.1158/2326-6066.cir-17-0498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Shevach EM, Thornton AM. tTregs, pTregs, and iTregs: similarities and differences. Immunol Rev. 2014;259(1):88–102. https://doi.org/10.1111/imr.12160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wei T, Zhong W, Li Q. Role of heterogeneous regulatory T cells in the tumor microenvironment. Pharmacol Res. 2020;153:104659. https://doi.org/10.1016/j.phrs.2020.104659.

    Article  PubMed  Google Scholar 

  25. Kamada T, Togashi Y, Tay C, Ha D, Sasaki A, Nakamura Y, Sato E, Fukuoka S, Tada Y, Tanaka A, Morikawa H, Kawazoe A, Kinoshita T, Shitara K, Sakaguchi S, Nishikawa H. PD-1(+) regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proc Natl Acad Sci U S A. 2019;116(20):9999–10008. https://doi.org/10.1073/pnas.1822001116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tokunaga R, Naseem M, Lo JH, Battaglin F, Soni S, Puccini A, Berger MD, Zhang W, Baba H, Lenz HJ. B cell and B cell-related pathways for novel cancer treatments. Cancer Treat Rev. 2019;73:10–9. https://doi.org/10.1016/j.ctrv.2018.12.001.

    Article  CAS  PubMed  Google Scholar 

  27. Yuen GJ, Demissie E, Pillai S. B lymphocytes and cancer: a love-hate relationship. Trends Cancer. 2016;2(12):747–57. https://doi.org/10.1016/j.trecan.2016.10.010.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Zhang CY, Xin H, Zhang W, Yazaki PJ, Zhang ZF, Le K, Li WZ, Lee H, Kwak L, Forman S, Jove R, Yu H. CD5 binds to interleukin-6 and induces a feed-forward loop with the transcription factor STAT3 in B cells to promote cancer. Immunity. 2016;44(4):913–23. https://doi.org/10.1016/j.immuni.2016.04.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Olkhanud PB, Damdinsuren B, Bodogai M, Gress RE, Sen R, Wejksza K, Malchinkhuu E, Wersto RP, Biragyn A. Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4(+) T cells to T-regulatory cells. Cancer Res. 2011;71(10):3505–15. https://doi.org/10.1158/0008-5472.CAN-10-4316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang SS, Liu W, Ly D, Xu H, Qu LM, Zhang L. Tumor-infiltrating B cells: their role and application in anti-tumor immunity in lung cancer. Cell Mol Immunol. 2019;16(1):6–18. https://doi.org/10.1038/s41423-018-0027-x.

    Article  CAS  PubMed  Google Scholar 

  31. Sharonov GV, Serebrovskaya EO, Yuzhakova DV, Britanova OV, Chudakov DM. B cells, plasma cells and antibody repertoires in the tumour microenvironment. Nat Rev Immunol. 2020; https://doi.org/10.1038/s41577-019-0257-x.

  32. Di Vito C, Mikulak J, Zaghi E, Pesce S, Marcenaro E, Mavilio D. NK cells to cure cancer. Semin Immunol. 2019;41:101272. https://doi.org/10.1016/j.smim.2019.03.004.

    Article  CAS  PubMed  Google Scholar 

  33. Lanier LL. Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol. 2008;9(5):495–502. https://doi.org/10.1038/ni1581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Close HJ, Wurdak H, Short SC, Melcher AA, Stead LF, Wilson EB, Cook GP. Natural killer cell recognition of glioblastoma. Immunology. 2014;143:138.

    Article  Google Scholar 

  35. Giorda R, Rudert WA, Vavassori C, Chambers WH, Hiserodt JC, Trucco M. NKR-P1, a signal transduction molecule on natural killer cells. Science. 1990;249(4974):1298–300.

    Article  CAS  Google Scholar 

  36. Zhu YT, Huang B, Shi J. Fas ligand and lytic granule differentially control cytotoxic dynamics of natural killer cell against cancer target. Oncotarget. 2016;7(30):47163–72. https://doi.org/10.18632/oncotarget.9980.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Fehniger TA, Cooper MA. Harnessing NK cell memory for cancer immunotherapy. Trends Immunol. 2016;37(12):877–88. https://doi.org/10.1016/j.it.2016.09.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Porta C, Riboldi E, Ippolito A, Sica A. Molecular and epigenetic basis of macrophage polarized activation. Semin Immunol. 2015;27(4):237–48. https://doi.org/10.1016/j.smim.2015.10.003.

    Article  CAS  PubMed  Google Scholar 

  39. Belgiovine C, D'Incalci M, Allavena P, Frapolli R. Tumor-associated macrophages and anti-tumor therapies: complex links. Cell Mol Life Sci. 2016;73(13):2411–24. https://doi.org/10.1007/s00018-016-2166-5.

    Article  CAS  PubMed  Google Scholar 

  40. Chittezhath M, Dhillon MK, Lim JY, Laoui D, Shalova IN, Teo YL, Chen J, Kamaraj R, Raman L, Lum J, Thamboo TP, Chiong E, Zolezzi F, Yang H, Van Ginderachter JA, Poidinger M, Wong AS, Biswas SK. Molecular profiling reveals a tumor-promoting phenotype of monocytes and macrophages in human cancer progression. Immunity. 2014;41(5):815–29. https://doi.org/10.1016/j.immuni.2014.09.014.

    Article  CAS  PubMed  Google Scholar 

  41. Dimitrios M. Naturally occurring regulatory T cells show reduced sensitivity toward oxidative stress-induced cell death. Blood. 2009;15:113.

    Google Scholar 

  42. King MR, Ismail AS, Davis LS, Karp DR. Oxidative stress promotes polarization of human T cell differentiation toward a T helper 2 phenotype. J Immunol. 2006;176(5):2765–72. https://doi.org/10.4049/jimmunol.176.5.2765.

    Article  CAS  PubMed  Google Scholar 

  43. Chen X, Song M, Zhang B, Zhang Y. Reactive oxygen species regulate T cell immune response in the tumor microenvironment. Oxidative Med Cell Longev. 2016;2016:1580967. https://doi.org/10.1155/2016/1580967.

    Article  CAS  Google Scholar 

  44. Cemerski S, van Meerwijk JPM, Romagnoli P. Oxidative-stress-induced T lymphocyte hyporesponsiveness is caused by structural modification rather than proteasomal degradation of crucial TCR signaling molecules. Eur J Immunol. 2003;33(8):2178–85. https://doi.org/10.1002/eji.200323898.

    Article  CAS  PubMed  Google Scholar 

  45. Mak TW, Saunders ME. 14 - T cell activation. In: Mak TW, Saunders ME, editors. The immune response. Burlington: Academic; 2006. p. 373–401. https://doi.org/10.1016/B978-012088451-3.50016-8.

    Chapter  Google Scholar 

  46. Cemerski S, Cantagrel A, van Meerwijk JPM, Romagnoli P. Reactive oxygen species differentially affect T cell receptor-signaling pathways. J Biol Chem. 2002;277(22):19585–93. https://doi.org/10.1074/jbc.M111451200.

    Article  CAS  PubMed  Google Scholar 

  47. Mizoguchi H. Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science. 1992;5089:258.

    Google Scholar 

  48. Otsuji M. Oxidative stress by tumor-derived macrophages suppresses the expression of CD3 zeta chain of T-cell receptor complex and antigen-specific T-cell responses. Proc Natl Acad Sci U S A. 1996;23:93.

    Google Scholar 

  49. Sukumar M, Liu J, Mehta GU, Patel SJ, Roychoudhuri R, Crompton JG, Klebanoff CA, Ji Y, Li P, Yu Z, Whitehill GD, Clever D, Eil RL, Palmer DC, Mitra S, Rao M, Keyvanfar K, Schrump DS, Wang E, Marincola FM, Gattinoni L, Leonard WJ, Muranski P, Finkel T, Restifo NP. Mitochondrial membrane potential identifies cells with enhanced stemness for cellular therapy. Cell Metab. 2016;23(1):63–76. https://doi.org/10.1016/j.cmet.2015.11.002.

    Article  CAS  PubMed  Google Scholar 

  50. Olmos Y, Valle I, Borniquel S, Tierrez A, Soria E, Lamas S, Monsalve M. Mutual dependence of Foxo3a and PGC-1alpha in the induction of oxidative stress genes. J Biol Chem. 2009;284(21):14476–84. https://doi.org/10.1074/jbc.M807397200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Scharping NE, Menk AV, Moreci RS, Whetstone RD, Dadey RE, Watkins SC, Ferris RL, Delgoffe GM. The tumor microenvironment represses T cell mitochondrial biogenesis to drive intratumoral T cell metabolic insufficiency and dysfunction. Immunity. 2016;45(2):374–88. https://doi.org/10.1016/j.immuni.2016.07.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Shen BC, Huang SC. Predominant Th2/Tc2 polarity of tumor-infiltrating lymphocytes in cervical cancer. Int J Gynecol Obstet. 2000;70:A62. https://doi.org/10.1016/S0020-7292(00)82673-9.

    Article  Google Scholar 

  53. Liang Z. Enhanced Th17 differentiation and aggravated arthritis in IEX-1-deficient mice by mitochondrial reactive oxygen species-mediated signaling. J Immunol. 2012;4:189.

    Google Scholar 

  54. Jeremias I. Inhibition of nuclear factor kappaB activation attenuates apoptosis resistance in lymphoid cells. Blood. 1998;12:91.

    Article  Google Scholar 

  55. Malmberg KJ. Inhibition of activated/memory (CD45RO(+)) T cells by oxidative stress associated with block of NF-kappaB activation. J Immunol. 2001;5:167.

    Google Scholar 

  56. Tang G, Minemoto Y, Dibling B, Purcell NH, Li Z, Karin M, Lin A. Inhibition of JNK activation through NF-κB target genes. Nature. 2001;414(6861):313–7. https://doi.org/10.1038/35104568.

    Article  CAS  PubMed  Google Scholar 

  57. Sankar B. Tumor-induced oxidative stress perturbs nuclear factor-kappaB activity-augmenting tumor necrosis factor-alpha-mediated T-cell death: protection by curcumin. Cancer Res. 2007;1:67.

    Google Scholar 

  58. Stuelten CH, Byfield SD, Arany PR, Karpova TS, Stetler-Stevenson WG, Roberts AB. Breast cancer cells induce stromal fibroblasts to express MMP-9 via secretion of TNF-α and TGF-β. J Cell Sci. 2005;118(10):2143. https://doi.org/10.1242/jcs.02334.

    Article  CAS  PubMed  Google Scholar 

  59. Bowie A. Oxidative stress and nuclear factor-kappaB activation: a reassessment of the evidence in the light of recent discoveries. Biochem Pharmacol. 2000;1:59.

    Google Scholar 

  60. Belikov AV, Schraven B, Simeoni L. T cells and reactive oxygen species. J Biomed Sci. 2015;22:85. https://doi.org/10.1186/s12929-015-0194-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Min L-W. Vitamin E inhibits CD95 ligand expression and protects T cells from activation-induced cell death. J Clin Invest. 2002;5:110.

    Google Scholar 

  62. Kiessling R, Wasserman K, Horiguchi S, Kono K, Sjöberg J, Pisa P, Petersson M. Tumor-induced immune dysfunction. Cancer Immun. 1999;48(7):353–62. https://doi.org/10.1007/s002620050586.

    Article  CAS  Google Scholar 

  63. Thor FB. Oxygen radicals induce poly(ADP-ribose) polymerase-dependent cell death in cytotoxic lymphocytes. J Immunol. 2006;176(12):7301–7.

    Article  Google Scholar 

  64. Kim EK, Seo HS, Chae MJ, Jeon IS, Song BY, Park YJ, Ahn HM, Yun CO, Kang CY. Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures. Gene Ther. 2014;21(1):106–14. https://doi.org/10.1038/gt.2013.65.

    Article  CAS  PubMed  Google Scholar 

  65. Hamilos DL, Zelarney P, Mascali JJ. Lymphocyte proliferation in glutathione-depleted lymphocytes: direct relationship between glutathione availability and the proliferative response. Immunopharmacology. 1989;18(3):223–35. https://doi.org/10.1016/0162-3109(89)90020-9.

    Article  CAS  PubMed  Google Scholar 

  66. Tanja H. The role of low molecular weight thiols in T lymphocyte proliferation and IL-2 secretion. J Immunol. 2005;1950(12):175.

    Google Scholar 

  67. Yan Z, Garg SK, Banerjee R. Regulatory T cells interfere with glutathione metabolism in dendritic cells and T cells. J Biol Chem. 2010;285(53):41525–32. https://doi.org/10.1074/jbc.M110.189944.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Suthanthiran M. Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens. Proc Natl Acad Sci U S A. 1990;9:87.

    Google Scholar 

  69. Messina JP. Cell cycle progression of glutathione-depleted human peripheral blood mononuclear cells is inhibited at S phase. J Immunol. 1989;6:143.

    Google Scholar 

  70. Debaprasad M. Failure in peripheral immuno-surveillance due to thymic atrophy: importance of thymocyte maturation and apoptosis in adult tumor-bearer. Life Sci. 2005;21:77.

    Google Scholar 

  71. Francisco B. NK cell metabolism and tumor microenvironment. Front Immunol. 2019;10:2278.

    Article  Google Scholar 

  72. Aydin E, Johansson J, Nazir FH, Hellstrand K, Martner A. Role of NOX2-derived reactive oxygen species in NK cell-mediated control of murine melanoma metastasis. Cancer Immunol Res. 2017;5:9.

    Article  Google Scholar 

  73. Mellqvist UH. Natural killer cell dysfunction and apoptosis induced by chronic myelogenous leukemia cells: role of reactive oxygen species and regulation by histamine. Blood. 2000;5:96.

    Google Scholar 

  74. Johan A. Monocytic AML cells inactivate antileukemic lymphocytes: role of NADPH oxidase/gp91(phox) expression and the PARP-1/PAR pathway of apoptosis. Blood. 2012;24:119.

    Google Scholar 

  75. Seong-Woon Y. Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science. 2002;5579:297.

    Google Scholar 

  76. Tentori L. Potential clinical applications of poly(ADP-ribose) polymerase (PARP) inhibitors. Pharmacol Res. 2002;2:45.

    Google Scholar 

  77. Fenerty KE, Padget M, Wolfson B, Gameiro SR, Su Z, Lee JH, Rabizadeh S, Soon-Shiong P, Hodge JW. Immunotherapy utilizing the combination of natural killer– and antibody dependent cellular cytotoxicity (ADCC)–mediating agents with poly (ADP-ribose) polymerase (PARP) inhibition. J Immunother Cancer. 2018;6:1.

    Article  Google Scholar 

  78. Tentori L. Chemopotentiation by PARP inhibitors in cancer therapy. Pharmacol Res. 2005;1:52.

    Google Scholar 

  79. Zhu H, Wang B, Kong L, An T, Li Y. Parvifoline AA promotes susceptibility of hepatocarcinoma to natural killer cell-mediated cytolysis by targeting peroxiredoxin. Cell Chem Biol. 2019;26:8.

    Article  Google Scholar 

  80. Sporn MB, Liby KT. NRF2 and cancer: the good, the bad and the importance of context. Nat Rev Cancer. 2012;12(8):564–71. https://doi.org/10.1038/nrc3278.

    Article  CAS  PubMed  Google Scholar 

  81. Maj T, Wang W, Crespo J, Zhang H, Wang W, Wei S, Zhao L, Vatan L, Shao I, Szeliga W, Lyssiotis C, Liu JR, Kryczek I, Zou W. Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor. Nat Immunol. 2017;18(12):1332–41. https://doi.org/10.1038/ni.3868.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Silvia D. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007;6:204.

    Google Scholar 

  83. Arvey A, van der Veeken J, Samstein RM, Feng Y, Stamatoyannopoulos JA, Rudensky AY. Inflammation-induced repression of chromatin bound by the transcription factor Foxp3 in regulatory T cells. Nat Immunol. 2014;15(6):580–7. https://doi.org/10.1038/ni.2868.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Faraaz BC. Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis. Nature. 2010;7317:467.

    Google Scholar 

  85. Reth M. Hydrogen peroxide as second messenger in lymphocyte activation. Nat Immunol. 2002;3(12):1129–34. https://doi.org/10.1038/ni1202-1129.

    Article  CAS  PubMed  Google Scholar 

  86. Salimi A, Roudkenar MH, Sadeghi L, Mohseni A, Seydi E, Pirahmadi N, Pourahmad J. Ellagic acid, a polyphenolic compound, selectively induces ROS-mediated apoptosis in cancerous B-lymphocytes of CLL patients by directly targeting mitochondria. Redox Biol. 2015;6:461–71. https://doi.org/10.1016/j.redox.2015.08.021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Kantner H-P, Warsch W, Delogu A, Bauer E, Esterbauer H, Casanova E, Sexl V, Stoiber D. ETV6/RUNX1 induces reactive oxygen species and drives the accumulation of DNA damage in B cells. Neoplasia. 2013;15(11):1292. https://doi.org/10.1593/neo.131310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Zhang H, Wang L, Chu Y. Reactive oxygen species: the signal regulator of B cell. Free Radic Biol Med. 2019;142:16–22. https://doi.org/10.1016/j.freeradbiomed.2019.06.004.

    Article  CAS  PubMed  Google Scholar 

  89. Cubillos-Ruiz JR, Silberman PC, Rutkowski MR, Chopra S, Perales-Puchalt A, Song M, Zhang S, Bettigole SE, Gupta D, Holcomb K, Ellenson LH, Caputo T, Lee AH, Conejo-Garcia JR, Glimcher LH. ER stress sensor XBP1 controls anti-tumor immunity by disrupting dendritic cell homeostasis. Cell. 2015;161(7):1527–38. https://doi.org/10.1016/j.cell.2015.05.025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Christina P. Crosstalk between advanced glycation and endoplasmic reticulum stress: emerging therapeutic targeting for metabolic diseases. J Clin Endocrinol Metab. 2012;7:97.

    Google Scholar 

  91. Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020; https://doi.org/10.1038/s41580-020-0230-3.

  92. Claudio H. Targeting the unfolded protein response in disease. Nat Rev Drug Discov. 2013;9:12.

    Google Scholar 

  93. Ann-Hwee L. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Biol. 2003;21:23.

    Google Scholar 

  94. Vladykovskaya E, Sithu SD, Haberzettl P, Wickramasinghe NS, Merchant ML, Hill BG, McCracken J, Agarwal A, Dougherty S, Gordon SA, Schuschke DA, Barski OA, O'Toole T, D’Souza SE, Bhatnagar A, Srivastava S. Lipid peroxidation product 4-hydroxy-trans-2-nonenal causes endothelial activation by inducing endoplasmic reticulum stress. J Biol Chem. 2012;287(14):11398–409. https://doi.org/10.1074/jbc.M111.320416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Negre-Salvayre A, Coatrieux C, Ingueneau C, Salvayre R. Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors. J Pharmacol. 2008;153(1):6–20. https://doi.org/10.1038/sj.bjp.0707395.

    Article  CAS  Google Scholar 

  96. Giannoni E, Parri M, Chiarugi P. EMT and oxidative stress: a bidirectional interplay affecting tumor malignancy. Antioxid Redox Signal. 2012;16(11):1248–63. https://doi.org/10.1089/ars.2011.4280.

    Article  CAS  PubMed  Google Scholar 

  97. Luput L, Licarete E, Sesarman A, Patras L, Costelalupei M, Banciu M. Tumor-associated macrophages favor C26 murine colon carcinoma cell proliferation in an oxidative stress-dependent manner. Oncol Rep. 2017;37(4):2472–80. https://doi.org/10.3892/or.2017.5466.

    Article  CAS  PubMed  Google Scholar 

  98. Mantovani A, Sica A. Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol. 2010;22(2):231–7. https://doi.org/10.1016/j.coi.2010.01.009.

    Article  CAS  PubMed  Google Scholar 

  99. Kuo C-L, Chou H-Y, Chiu Y-C, Cheng AN, Fan C-C, Chang Y-N, Chen C-H, Jiang SS, Chen N-J, Lee AY-L. Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis. Cancer Lett. 2020;474:138–50. https://doi.org/10.1016/j.canlet.2020.01.019.

    Article  CAS  PubMed  Google Scholar 

  100. Dai E, Han L, Liu J, Xie Y, Kroemer G, Klionsky DJ, Zeh HJ, Kang R, Wang J, Tang D. Autophagy-dependent ferroptosis drives tumor-associated macrophage polarization via release and uptake of oncogenic KRAS protein. Autophagy. 2020; https://doi.org/10.1080/15548627.2020.1714209.

  101. Zuo L, He F, Sergakis GG, Koozehchian MS, Stimpfl JN, Rong Y, Diaz PT, Best TM. Interrelated role of cigarette smoking, oxidative stress, and immune response in COPD and corresponding treatments. Am J Phys. 2014;307(3):L205–18. https://doi.org/10.1152/ajplung.00330.2013.

    Article  CAS  Google Scholar 

  102. Kurze AK, Buhs S, Eggert D, Oliveira-Ferrer L, Muller V, Niendorf A, Wagener C, Nollau P. Immature O-glycans recognized by the macrophage glycoreceptor CLEC10A (MGL) are induced by 4-hydroxy-tamoxifen, oxidative stress and DNA-damage in breast cancer cells. Cell Commun Signal. 2019;17(1):107. https://doi.org/10.1186/s12964-019-0420-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Tang J, Ramis-Cabrer D, Wang XJ, Barreiro E. Immunotherapy with monoclonal antibodies in lung cancer of mice: oxidative stress and other biological events. Cancer. 2019;11:9.

    Google Scholar 

  104. Cubillos-Ruiz JR, Bettigole SE, Glimcher LH. Tumorigenic and immunosuppressive effects of endoplasmic reticulum stress in cancer. Cell. 2017;168(4):692–706. https://doi.org/10.1016/j.cell.2016.12.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Ohl K, Tenbrock K. Reactive oxygen species as regulators of MDSC-mediated immune suppression. Front Immunol. 2018;9:2499. https://doi.org/10.3389/fimmu.2018.02499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Sheng KC. Inflammatory mediators hold the key to dendritic cell suppression and tumor progression. Curr Med Chem. 2011;36:18.

    CAS  Google Scholar 

  107. Duan H. Novel therapeutic strategies for solid tumor based on body’s intrinsic antitumor immune system. Cell Physiol Biochem. 2018;47(2):441–57. https://doi.org/10.1159/000489979.

    Article  CAS  PubMed  Google Scholar 

  108. Panda AK, Chakraborty D, Sarkar I, Khan T, Sa G. New insights into therapeutic activity and anticancer properties of curcumin. J Exp Pharmacol. 2017;9:31–45. https://doi.org/10.2147/JEP.S70568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Bhattacharyya S, Md Sakib Hossain D, Mohanty S, Sankar Sen G, Chattopadhyay S, Banerjee S, Chakraborty J, Das K, Sarkar D, Das T, Sa G. Curcumin reverses T cell-mediated adaptive immune dysfunctions in tumor-bearing hosts. Cell Mol Immunol. 2010;7(4):306–15. https://doi.org/10.1038/cmi.2010.11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Noweeda M. All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res. 2006;18:66.

    Google Scholar 

  111. Zhang Y, Choksi S, Chen K, Pobezinskaya Y, Linnoila I, Liu Z-G. ROS play a critical role in the differentiation of alternatively activated macrophages and the occurrence of tumor-associated macrophages. Cell Res. 2013;23(7):898–914. https://doi.org/10.1038/cr.2013.75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Orsolic N, Kunstic M, Kukolj M, Gracan R, Nemrava J. Oxidative stress, polarization of macrophages and tumour angiogenesis: efficacy of caffeic acid. Chem Biol Interact. 2016;256:111–24. https://doi.org/10.1016/j.cbi.2016.06.027.

    Article  CAS  PubMed  Google Scholar 

  113. Netea-Maier RT, Smit JWA, Netea MG. Metabolic changes in tumor cells and tumor-associated macrophages: a mutual relationship. Cancer Lett. 2018;413:102–9. https://doi.org/10.1016/j.canlet.2017.10.037.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, PR China

    Yuexi Wang, Yanan Hu, Yuting Jiang & Shengtao Zhou

  2. College of Life Science, Sichuan University, Chengdu, PR China

    Yuexi Wang & Yanan Hu

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  1. Yuexi Wang
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  2. Yanan Hu
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  3. Yuting Jiang
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  4. Shengtao Zhou
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  1. Basic Medical Science & Forensic Medicine, West China Hospital of Sichuan University, Chengdu, China

    Canhua Huang

  2. Department of Pharmacology, West China Hospital of Sichuan University, Chengdu, China

    Yuanyuan Zhang

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Wang, Y., Hu, Y., Jiang, Y., Zhou, S. (2021). Oxidative Stress in the Tumor Immune Microenvironment. In: Huang, C., Zhang, Y. (eds) Oxidative Stress. Springer, Singapore. https://doi.org/10.1007/978-981-16-0522-2_2

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