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Approaches to Immunologic Monitoring of Clinical Trials

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The Tumor Immunoenvironment

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Abstract

Performance of thoughtful immunologic monitoring is critical to the conduct of an immune-based clinical trial. In the absence of high frequencies of significant clinical responses, immunologic responses may be the primary basis for understanding the outcomes of the intervention tested. In addition, important immunologic changes may occur from non-immunologic interventions like surgery, chemotherapy and radiotherapy. These standard-of-care treatments may promote or inhibit anti-tumor immunity. Measurement of these changes can yield important insights into the mechanism of clinical responses in patients.

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References

  • Adotevi O, Pere H, Ravel P, Haicheur N, Badoual C, Merillon N, Medioni J, Peyrard S, Roncelin S, Verkarre V, Mejean A, Fridman WH et al (2010) A decrease of regulatory T cells correlates with overall survival after sunitinib-based antiangiogenic therapy in metastatic renal cancer patients. J Immunother 33:991–998

    Article  PubMed  CAS  Google Scholar 

  • Albers AE, Ferris RL, Kim GG, Chikamatsu K, de Leo AB, Whiteside TL (2005) Immune responses to p53 in patients with cancer: enrichment in tetramer +p53 peptide-specific T cells and regulatory T cells at tumor sites. Cancer Immunol Immunother 54:1072–1081

    Article  PubMed  CAS  Google Scholar 

  • Andoniou CE, Coudert JD, Degli-Esposti MA (2008) Killers and beyond: NK-cell-mediated control of immune responses. Eur J Immunol 38:2938–2942

    Article  PubMed  CAS  Google Scholar 

  • Andrews DM, Scalzo AA, Yokoyama WM, Smyth MJ, Degli-Esposti MA (2003) Functional interactions between dendritic cells and NK cells during viral infection. Nat Immunol 4:175–181

    Article  PubMed  CAS  Google Scholar 

  • Appay V (2004) The physiological role of cytotoxic CD4+ T-cells: the holy grail? Clin Exp Immunol 138:10–13

    Article  PubMed  CAS  Google Scholar 

  • Asai T, Storkus WJ, Whiteside TL (2000) Evaluation of the modified ELISPOT assay for gamma interferon production in cancer patients receiving antitumor vaccines. Clin Diagn Lab Immunol 7:145–154

    PubMed  CAS  Google Scholar 

  • Ayaru L, Pereira SP, Alisa A, Pathan AA, Williams R, Davidson B, Burroughs AK, Meyer T, Behboudi S (2007) Unmasking of alpha-fetoprotein-specific CD4(+) T cell responses in hepatocellular carcinoma patients undergoing embolization. J Immunol 178:1914–1922

    PubMed  CAS  Google Scholar 

  • Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay NEH, Mosseri V, Laccourreye O, Bruneval P, Fridman WH, Brasnu DF, Tartour E (2006) Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res 12:465–472

    Article  PubMed  CAS  Google Scholar 

  • Banchereau J, Palucka AK (2005) Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 5:296–306

    Article  PubMed  CAS  Google Scholar 

  • Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252

    Article  PubMed  CAS  Google Scholar 

  • Banchereau J, Palucka AK, Dhodapkar M, Burkeholder S, Taquet N, Rolland A, Taquet S, Coquery S, Wittkowski KM, Bhardwaj N, Pineiro L, Steinman R et al (2001) Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dendritic cell vaccine. Cancer Res 61:6451–6458

    PubMed  CAS  Google Scholar 

  • Bastarache JA, Koyama T, Wickersham NE, Mitchell DB, Mernaugh RL, Ware LB (2011) Accuracy and reproducibility of a multiplex immunoassay platform: a validation study. J Immunol Methods 367:33–39

    Article  PubMed  CAS  Google Scholar 

  • Bedognetti D, Balwit JM, Wang E, Disis ML, Britten CM, Delogu LG, Tomei S, Fox BA, Gajewski TF, Marincola FM, Butterfield LH (2011) SITC/iSBTc cancer immunotherapy biomarkers resource document: online resources and useful tools—a compass in the land of biomarker discovery. J Transl Med 9:155

    Article  PubMed  CAS  Google Scholar 

  • Bennouna J, Hildesheim A, Chikamatsu K, Gooding W, Storkus WJ, Whiteside TL (2002) Application of IL-5 ELISPOT assays to quantification of antigen-specific T helper responses. J Immunol Methods 261:145–156

    Article  PubMed  CAS  Google Scholar 

  • Bergmann C, Strauss L, Zeidler R, Lang S, Whiteside TL (2007) Expansion and characteristics of human T regulatory type 1 cells in co-cultures simulating tumor microenvironment. Cancer Immunol Immunother 56:1429–1442

    Article  PubMed  Google Scholar 

  • Bergmann C, Strauss L, Wang Y, Szczepanski MJ, Lang S, Johnson JT, Whiteside TL (2008) T regulatory type 1 cells in squamous cell carcinoma of the head and neck: mechanisms of suppression and expansion in advanced disease. Clin Cancer Res 14:3706–3715

    Article  PubMed  CAS  Google Scholar 

  • Bibeau F, Lopez-Crapez E, di Fiore F, Thezenas S, Ychou M, Blanchard F, Lamy A, Penault-Llorca F, Frebourg T, Michel P, Sabourin JC, Boissiere-Michot F (2009) Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J Clin Oncol 27:1122–1129

    Article  PubMed  CAS  Google Scholar 

  • Boon T, van der Bruggen P (1996) Human tumor antigens recognized by T lymphocytes. J Exp Med 183:725–729

    Article  PubMed  CAS  Google Scholar 

  • Boon T, Coulie PG, van den Eynde BJ, van der Bruggen P (2006) Human T cell responses against melanoma. Annu Rev Immunol 24:175–208

    Article  PubMed  CAS  Google Scholar 

  • Borg C, Jalil A, Laderach D, Maruyama K, Wakasugi H, Charrier S, Ryffel B, Cambi A, Figdor C, Vainchenker W, Galy A, Caignard A et al (2004) NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs. Blood 104:3267–3275

    Article  PubMed  CAS  Google Scholar 

  • Bos R, Sherman LA (2010) CD4+ T-cell help in the tumor milieu is required for recruitment and cytolytic function of CD8+ T lymphocytes. Cancer Res 70:8368–8377

    Article  PubMed  CAS  Google Scholar 

  • Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465

    Article  PubMed  CAS  Google Scholar 

  • Britten CM, Gouttefangeas C, Welters MJ, Pawelec G, Koch S, Ottensmeier C, Mander A, Walter S, Paschen A, Muller-Berghaus J, Haas I, Mackensen A et al (2008) The CIMT-monitoring panel: a two-step approach to harmonize the enumeration of antigen-specific CD8+ T lymphocytes by structural and functional assays. Cancer Immunol Immunother 57:289–302

    Article  PubMed  CAS  Google Scholar 

  • Britten CM, Janetzki S, van der Burg SH, Huber C, Kalos M, Levitsky HI, Maecker HT, Melief CJ, O’Donnell-Tormey J, Odunsi K, Old LJ, Pawelec G et al (2011) Minimal information about T cell assays: the process of reaching the community of T cell immunologists in cancer and beyond. Cancer Immunol Immunother 60:15–22

    Article  PubMed  CAS  Google Scholar 

  • Britten CM, Janetzki S, Butterfield LH, Ferrari G, Gouttefangeas C, Huber C, Kalos M, Levitsky HI, Maecker HT, Melief CJ, O’Donnell-Tormey J, Odunsi K et al (2012) T cell assays and MIATA: the essential minimum for maximum impact. Immunity 37:1–2

    Article  PubMed  CAS  Google Scholar 

  • Butterfield LH, Ribas A, Dissette VB, Amarnani SN, Vu HT, Oseguera D, Wang HJ, Elashoff RM, McBride WH, Mukherji B, Cochran AJ, Glaspy JA et al (2003a) Determinant spreading associated with clinical response in dendritic cell-based immunotherapy for malignant melanoma. Clin Cancer Res 9:998–1008

    PubMed  CAS  Google Scholar 

  • Butterfield LH, Ribas A, Meng WS, Dissette VB, Amarnani S, Vu HT, Seja E, Todd K, Glaspy JA, McBride WH, Economou JS (2003b) T-cell responses to HLA-A*0201 immunodominant peptides derived from alpha-fetoprotein in patients with hepatocellular cancer. Clin Cancer Res 9:5902–5908

    PubMed  CAS  Google Scholar 

  • Butterfield LH, Comin-Anduix B, Vujanovic L, Lee Y, Dissette VB, Yang JQ, Vu HT, Seja E, Oseguera DK, Potter DM, Glaspy JA, Economou JS et al (2008a) Adenovirus MART-1-engineered autologous dendritic cell vaccine for metastatic melanoma. J Immunother 31:294–309

    Article  PubMed  Google Scholar 

  • Butterfield LH, Disis ML, Fox BA, Lee PP, Khleif SN, Thurin M, Trinchieri G, Wang E, Wigginton J, Chaussabel D, Coukos G, Dhodapkar M et al (2008b) A systematic approach to biomarker discovery; preamble to “the iSBTc-FDA taskforce on immunotherapy biomarkers”. J Transl Med 6:81

    Article  PubMed  Google Scholar 

  • Butterfield LH, Gooding W, Whiteside TL (2008c) Development of a potency assay for human dendritic cells: IL-12p70 production. J Immunother 31:89–100

    Article  PubMed  CAS  Google Scholar 

  • Butterfield LH, Disis ML, Khleif SN, Balwit JM, Marincola FM (2010) Immuno-oncology biomarkers 2010 and beyond: perspectives from the iSBTc/SITC biomarker task force. J Transl Med 8:130

    Article  PubMed  Google Scholar 

  • Butterfield LH, Palucka AK, Britten CM, Dhodapkar MV, Hakansson L, Janetzki S, Kawakami Y, Kleen TO, Lee PP, Maccalli C, Maecker HT, Maino VC et al (2011a) Recommendations from the iSBTc-SITC/FDA/NCI workshop on immunotherapy biomarkers. Clin Cancer Res 17:3064–3076

    Article  PubMed  CAS  Google Scholar 

  • Butterfield LH, Potter DM, Kirkwood JM (2011b) Multiplex serum biomarker assessments: technical and biostatistical issues. J Transl Med 9:173

    Article  PubMed  CAS  Google Scholar 

  • Chaturvedi AK, Kemp TJ, Pfeiffer RM, Biancotto A, Williams M, Munuo S, Purdue MP, Hsing AW, Pinto L, McCoy JP, Hildesheim A (2011) Evaluation of multiplexed cytokine and inflammation marker measurements: a methodologic study. Cancer Epidemiol Biomarkers Prev 20:1902–1911

    Article  PubMed  CAS  Google Scholar 

  • Clemente CG, Mihm MCJ, Bufalino R, Zurrida S, Collini P, Cascinelli N (1996) Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 77:1303–1310

    Article  PubMed  CAS  Google Scholar 

  • Crotzer VL, Blum JS (2010) Autophagy and adaptive immunity. Immunology 131:9–17

    Article  PubMed  CAS  Google Scholar 

  • Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949

    Article  PubMed  CAS  Google Scholar 

  • Daud AI, Mirza N, Lenox B, Andrews S, Urbas P, Gao GX, Lee JH, Sondak VK, Riker AI, Deconti RC, Gabrilovich D (2008) Phenotypic and functional analysis of dendritic cells and clinical outcome in patients with high-risk melanoma treated with adjuvant granulocyte macrophage colony-stimulating factor. J Clin Oncol 26:3235–3241

    Article  PubMed  CAS  Google Scholar 

  • de Jager W, Bourcier K, Rijkers GT, Prakken BJ, Seyfert-Margolis V (2009) Prerequisites for cytokine measurements in clinical trials with multiplex immunoassays. BMC Immunol 10:52

    Article  PubMed  CAS  Google Scholar 

  • de Kruijf EM, van Nes JG, Sajet A, Tummers QR, Putter H, Osanto S, Speetjens FM, Smit VT, Liefers GJ, van de Velde CJ, Kuppen PJ (2010) The predictive value of HLA class I tumor cell expression and presence of intratumoral Tregs for chemotherapy in patients with early breast cancer. Clin Cancer Res 16:1272–1280

    Article  PubMed  CAS  Google Scholar 

  • Della Bella S, Gennaro M, Vaccari M, Ferraris C, Nicola S, Riva A, Clerici M, Greco M, Villa ML (2003) Altered maturation of peripheral blood dendritic cells in patients with breast cancer. Br J Cancer 89:1463–1472

    Article  PubMed  CAS  Google Scholar 

  • Denkert C, Loibl S, Noske A, Roller M, Muller BM, Komor M, Budczies J, Darb-Esfahani S, Kronenwett R, Hanusch C, von Torne C, Weichert W et al (2010) Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28:105–113

    Article  PubMed  CAS  Google Scholar 

  • Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58:49–59

    Article  PubMed  CAS  Google Scholar 

  • Disis ML (2011) Immunologic biomarkers as correlates of clinical response to cancer immunotherapy. Cancer Immunol Immunother 60:433–442

    Article  PubMed  CAS  Google Scholar 

  • Disis ML, Gooley TA, Rinn K, Davis D, Piepkorn M, Cheever MA, Knutson KL, Schiffman K (2002) Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J Clin Oncol 20:2624–2632

    Article  PubMed  CAS  Google Scholar 

  • Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A 90:3539–3543

    Article  PubMed  CAS  Google Scholar 

  • Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M et al (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298:850–854

    Article  PubMed  CAS  Google Scholar 

  • Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, Rogers LJ, Gracia GJ et al (2005) Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 23:2346–2357

    Article  PubMed  CAS  Google Scholar 

  • Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, Wunderlich J, Restifo NP et al (2008) Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol 26:5233–5239

    Article  PubMed  CAS  Google Scholar 

  • Eckl J, Buchner A, Prinz PU, Riesenberg R, Siegert SI, Kammerer R, Nelson PJ, Noessner E (2012) Transcript signature predicts tissue NK cell content and defines renal cell carcinoma subgroups independent of TNM staging. J Mol Med (Berl) 90:55–66

    Article  CAS  Google Scholar 

  • Erdag G, Schaefer JT, Smolkin ME, Deacon DH, Shea SM, Dengel LT, Patterson JW, Slingluff CL Jr (2012) Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma. Cancer Res 72:1070–1080

    Article  PubMed  CAS  Google Scholar 

  • Eruslanov E, Neuberger M, Daurkin I, Perrin GQ, Algood C, Dahm P, Rosser C, Vieweg J, Gilbert SM, Kusmartsev S (2012) Circulating and tumor-infiltrating myeloid cell subsets in patients with bladder cancer. Int J Cancer 130:1109–1119

    Article  PubMed  CAS  Google Scholar 

  • Fallarino F, Grohmann U, Bianchi R, Vacca C, Fioretti MC, Puccetti P (2000) Th1 and Th2 cell clones to a poorly immunogenic tumor antigen initiate CD8+ T cell-dependent tumor eradication in vivo. J Immunol 165:5495–5501

    PubMed  CAS  Google Scholar 

  • Ferlazzo G, Munz C (2004) NK cell compartments and their activation by dendritic cells. J Immunol 172:1333–1339

    PubMed  CAS  Google Scholar 

  • Ferlazzo G, Tsang ML, Morretta L, Melioli G, Steinman RM, Munz C (2002) Human dendritic cells activate resting natural killer (NK) cells and are recognized via NKp30 receptor by activated NK cells. J Exp Med 195:343–351

    Article  PubMed  CAS  Google Scholar 

  • Fernandez NC, Lozier A, Flament C, Ricciardi-Castagnoli P, Bellet D, Suter M (1999) Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nature Med 5:405–411

    Article  PubMed  CAS  Google Scholar 

  • Ferris RL, Jaffee EM, Ferrone S (2010) Tumor antigen-targeted, monoclonal antibody-based immunotherapy: clinical response, cellular immunity, and immunoescape. J Clin Oncol 28:4390–4399

    Article  PubMed  CAS  Google Scholar 

  • Filipazzi P, Valenti R, Huber V, Pilla L, Canese P, Iero M, Castelli C, Mariani L, Parmiani G, Rivoltini L (2007) Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol 25:2546–2553

    Article  PubMed  CAS  Google Scholar 

  • Filipazzi P, Huber V, Rivoltini L (2011) Phenotype, function and clinical implications of myeloid-derived suppressor cells in cancer patients. Cancer Immunol Immunother 61:255–263

    Article  PubMed  CAS  Google Scholar 

  • Finkelstein SE, Carey T, Fricke I, Yu D, Goetz D, Gratz M, Dunn M, Urbas P, Daud A, DeConti R, Antonia S, Gabrilovich D et al (2010) Changes in dendritic cell phenotype after a new high-dose weekly schedule of interleukin-2 therapy for kidney cancer and melanoma. J Immunother 33:817–827

    Article  PubMed  CAS  Google Scholar 

  • Fox BA, Schendel DJ, Butterfield LH, Aamdal S, Allison JP, Ascierto PA, Atkins MB, Bartunkova J, Bergmann L, Berinstein N, Bonorino CC, Borden E et al (2011) Defining the critical hurdles in cancer immunotherapy. J Transl Med 9:214

    Article  PubMed  Google Scholar 

  • Fridman WH, Pages F, Sautes-Fridman C, Galon J (2012) The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 12:298–306

    Article  PubMed  CAS  Google Scholar 

  • Friedman KM, Prieto PA, Devillier LE, Gross CA, Yang JC, Wunderlich JR, Rosenberg SA, Dudley ME (2012) Tumor-specific CD4+ melanoma tumor-infiltrating lymphocytes. J Immunother 35:400–408 10.1097/CJI.0b013e31825898c5

    Google Scholar 

  • Gabitass RF, Annels NE, Stocken DD, Pandha HA, Middleton GW (2011) Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol Immunother 60:1419–1430

    Article  PubMed  CAS  Google Scholar 

  • Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12:253–268

    Article  PubMed  CAS  Google Scholar 

  • Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoue F, Bruneval P et al (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313:1960–1964

    Article  PubMed  CAS  Google Scholar 

  • Gavin MA, Torgerson TR, Houston E, DeRoos P, Ho WY, Stray-Pedersen A, Ocheltree EL, Greenberg PD, Ochs HD, Rudensky AY (2006) Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc Natl Acad Sci U S A 103:6659–6664

    Article  PubMed  CAS  Google Scholar 

  • Gerosa F, Baldani-Guerra B, Nisii C, Marchesini V, Carra G, Trinchieri G (2002) Reciprocal activating interaction between natural killer cells and dendritic cells. J Exp Med 195:327–333

    Article  PubMed  CAS  Google Scholar 

  • Gogas H, Ioannovich J, Dafni U, Stavropoulou-Giokas C, Frangia K, Tsoutsos D, Panagiotou P, Polyzos A, Papadopoulos O, Stratigos A, Markopoulos C, Bafaloukos D et al (2006) Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med 354:709–718

    Article  PubMed  CAS  Google Scholar 

  • Gumus E, Erdamar S, Demirel G, Horasanli K, Kendirci M, Miroglu C (2004) Association of positive serum anti-p53 antibodies with poor prognosis in bladder cancer patients. Int J Urol 11:1070–1077

    Article  PubMed  Google Scholar 

  • Gupta A, Probst HC, Vuong V, Landshammer A, Muth S, Yagita H, Schwendener R, Pruschy M, Knuth A, van den Broek M (2012) Radiotherapy promotes tumor-specific effector CD8+ T cells via dendritic cell activation. J Immunol 189:558–566

    Article  PubMed  CAS  Google Scholar 

  • Halama N, Braun M, Kahlert C, Spille A, Quack C, Rahbari N, Koch M, Weitz J, Kloor M, Zoernig I, Schirmacher P, Brand K et al (2011a) Natural killer cells are scarce in colorectal carcinoma tissue despite high levels of chemokines and cytokines. Clin Cancer Res 17:678–689

    Article  PubMed  CAS  Google Scholar 

  • Halama N, Michel S, Kloor M, Zoernig I, Benner A, Spille A, Pommerencke T, von Knebel DM, Folprecht G, Luber B, Feyen N, Martens UM et al (2011b) Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res 71:5670–5677

    Article  PubMed  CAS  Google Scholar 

  • Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K, Higuchi T, Yagi H, Takakura K, Minato N, Honjo T, Fujii S (2007) Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci 104:3360–3365

    Article  PubMed  CAS  Google Scholar 

  • Hamid O, Varterasian ML, Wadler S, Hecht JR, Benson A 3rd, Galanis E, Uprichard M, Omer C, Bycott P, Hackman RC, Shields AF (2003) Phase II trial of intravenous CI-1042 in patients with metastatic colorectal cancer. J Clin Oncol 21:1498–1504

    Article  PubMed  CAS  Google Scholar 

  • Harlin H, Meng Y, Peterson AC, Zha Y, Tretiakova M, Slingluff C, McKee M, Gajewski TF (2009) Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res 69:3077–3085

    Article  PubMed  CAS  Google Scholar 

  • Hayakawa Y, Screpanti V, Yagita H, Grandien A, Ljunggren HG, Smith MJ, Chambers BJ (2004) NK cell TRAIL eliminates immature dendritic cells in vivo and limits dendritic cell vaccination efficacy. J Immunol 172:123–129

    PubMed  CAS  Google Scholar 

  • Higano CS, Corman JM, Smith DC, Centeno AS, Steidle CP, Gittleman M, Simons JW, Sacks N, Aimi J, Small EJ (2008) Phase 1/2 dose-escalation study of a GM-CSF-secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer. Cancer 113:975–984

    Article  PubMed  CAS  Google Scholar 

  • Hiraoka K, Miyamoto M, Cho Y, Suzuoki M, Oshikiri T, Nakakubo Y, Itoh T, Ohbuchi T, Kondo S, Katoh H (2006) Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer 94:275–280

    Article  PubMed  CAS  Google Scholar 

  • Hung KRH, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H (1998) The central role of CD4+ T cells in the antitumor immune response. J Exp Med 188:2357–2368

    Article  PubMed  CAS  Google Scholar 

  • Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K (2000) Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11 year follow-up study of a general population. Lancet 356:1795–1799

    Article  PubMed  CAS  Google Scholar 

  • Janetzki S, Britten CM, Kalos M, Levitsky HI, Maecker HT, Melief CJ, Old LJ, Romero P, Hoos A, Davis MM (2009) “MIATA”-minimal information about T cell assays. Immunity 31:527–528

    Article  PubMed  CAS  Google Scholar 

  • Janetzki S, Price L, Britten CM, van der Burg SH, Caterini J, Currier JR, Ferrari G, Gouttefangeas C, Hayes P, Kaempgen E, Lennerz V, Nihlmark K et al (2010) Performance of serum-supplemented and serum-free media in IFNgamma Elispot assays for human T cells. Cancer Immunol Immunother 59:609–618

    Article  PubMed  CAS  Google Scholar 

  • Janssen EM, Droin NM, Lemmens EE, Pinkoski MJ, Bensinger SJ, Ehst BD, Griffith TS, Green DR, Schoenberger SP (2005) CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death. Nature 434:88–93

    Article  PubMed  CAS  Google Scholar 

  • Jinushi M, Takehara T, Kanto T, Tatsumi T, Groh V, Spies T, Miyagi T, Suzuki T, Sasaki Y, Hayashi N (2003) Critical role of MHC class I-related chain A and B expression on IFN-alpha stimulated dendritic cells in NK cell activation: Impairment in chronic hepatitis C virus infection. J Immunol 170:1249–1256

    PubMed  CAS  Google Scholar 

  • Kalinski P, Vieira PL, Schuitemaker JH, de Jong EC, Kapsenberg ML (2001) Prostaglandin E(2) is a selective inducer of interleukin-12 p40 (IL-12p40) production and an inhibitor of bioactive IL-12p70 heterodimer. Blood 97:3466–3469

    Article  PubMed  CAS  Google Scholar 

  • Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW et al (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363:411–422

    Article  PubMed  CAS  Google Scholar 

  • Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, van der Berends-Meer DM, Vloon AP, Essahsah F, Fathers LM, Offringa R, Drijfhout JW, Wafelman AR, Oostendorp J (2009) Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med 361:1838–1847

    Article  PubMed  CAS  Google Scholar 

  • Khan SS, Smith MS, Reda D, Suffredini AF, McCoy JP Jr (2004) Multiplex bead array assays for detection of soluble cytokines: comparisons of sensitivity and quantitative values among kits from multiple manufacturers. Cytometry B Clin Cytom 61:35–39

    Article  PubMed  CAS  Google Scholar 

  • Kiertscher SM, Gitlitz BJ, Figlin RA, Roth MD (2003) Granulocyte/macrophage-colony stimulating factor and interleukin-4 expand and activate type-1 dendritic cells (DC1) when administered in vivo to cancer patients. Int J Cancer 107:256–261

    Article  PubMed  CAS  Google Scholar 

  • Kim GG, Donnenberg VS, Donnenberg AD, Gooding W, Whiteside TL (2007) A novel multiparametric flow cytometry-based cytotoxicity assay simultaneously immunophenotypes effector cells: Comparisons to a 4 h 51Cr-release assay. J Immunol Methods 325:51–66

    Article  PubMed  CAS  Google Scholar 

  • Kirkwood JM, Butterfield LH, Tarhini AA, Zarour H, Kalinski P, Ferrone S (2012) Immunotherapy of cancer in 2012. CA Cancer J Clin 62(5):309–335

    Article  PubMed  Google Scholar 

  • Kirkwood JM, Lee S, Moschos SJ, Albertini MR, Michalak JC, Sander C, Whiteside T, Butterfield LH, Weiner L (2009) Immunogenicity and antitumor effects of vaccination with peptide vaccine ± granulocyte-monocyte colony-stimulating factor and/or IFN-alpha2b in advanced metastatic melanoma: Eastern cooperative oncology group phase II trial E1696. Clin Cancer Res 15:1443–1451

    Article  PubMed  CAS  Google Scholar 

  • Kotsakis A, Harasymczuk M, Schilling B, Georgoulias V, Argiris A, Whiteside TL (2012) Myeloid-derived suppressor cell measurements in fresh and cryopreserved blood samples. J Immunol Methods 381:14–22

    Article  PubMed  CAS  Google Scholar 

  • Krauze MT, Tarhini A, Gogas H, Kirkwood JM (2011) Prognostic significance of autoimmunity during treatment of melanoma with interferon. Semin Immunopathol 33:385–391

    Article  PubMed  CAS  Google Scholar 

  • Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S, Huang E, Finlayson E, Simeone D, Welling TH, Chang A, Coukos G et al (2009) Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114:1141–1149

    Article  PubMed  CAS  Google Scholar 

  • Ladoire S, Mignot G, Dabakuyo S, Arnould L, Apetoh L, Rebe C, Coudert B, Martin F, Bizollon MH, Vanoli A, Coutant C, Fumoleau P et al (2011) In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival. J Pathol 224:389–400

    Article  PubMed  CAS  Google Scholar 

  • Lai CL, Tsai CM, Tsai TT, Kuo BI, Chang KT, Fu HT, Perng RP, Chen JY (1998) Presence of serum anti-p53 antibodies is associated with pleural effusion and poor prognosis in lung cancer patients. Clin Cancer Res 4:3025–3030

    PubMed  CAS  Google Scholar 

  • Liakou CI, Kamat A, Tang DN, Chen H, Sun J, Troncoso P, Logothetis C, Sharma P (2008) CTLA-4 blockade increases IFNgamma-producing CD4+ ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc Natl Acad Sci U S A 105:14987–14992

    Article  PubMed  CAS  Google Scholar 

  • Lieberman J (2003) The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal. Nat Rev Immunol 3:361–370

    Article  PubMed  CAS  Google Scholar 

  • Liu D, O’Day SJ, Yang D, Boasberg P, Milford R, Kristedja T, Groshen S, Weber J (2005) Impact of gene polymorphisms on clinical outcome for stage IV melanoma patients treated with biochemotherapy: an exploratory study. Clin Cancer Res 11:1237–1246

    PubMed  CAS  Google Scholar 

  • Mahmoud SMA, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AHS, Ellis IO, Green AR (2011) Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Onc 29:1949–1955

    Article  Google Scholar 

  • Mailliard RB, Egawa S, Cai Q, Kalinska A, Bykovskaya SN, Lotze MT, Kapsenberg ML, Storkus WJ, Kalinski P (2002) Complementary dendritic cell-activating function of CD8+ and CD4+ T cells: helper role of CD8+ T cells in the development of T helper type 1 responses. J Exp Med 195:473–483

    Article  PubMed  CAS  Google Scholar 

  • Mailliard RB, Wankowicz-Kalinska A, Cai Q, Wesa A, Hilkens CM, Kapsenberg ML, Kirkwood JM, Storkus WJ, Kalinski P (2004) Alpha-type-1 polarized dendritic cells: a novel immunization tool with optimized CTL-inducing activity. Cancer Res 64:5934–5937

    Article  PubMed  CAS  Google Scholar 

  • Malyguine A, Umansky V, Shurin MR (2009) Cancer immunotherapy and immunomonitoring (CITIM): redefining cancer therapy. J Immunotoxicol 6:205–208

    Article  PubMed  Google Scholar 

  • Mander A, Gouttefangeas C, Ottensmeier C, Welters MJ, Low L, van der Burg SH, Britten CM (2010) Serum is not required for ex vivo IFN-gamma ELISPOT: a collaborative study of different protocols from the European CIMT immunoguiding program. Cancer Immunol Immunother 59:619–627

    Article  PubMed  CAS  Google Scholar 

  • Mandruzzato S, Solito S, Falisi E, Francescato S, Chiarion-Sileni V, Mocellin S, Zanon A, Rossi CR, Nitti D, Bronte V, Zanovello P (2009) IL4Ralpha+ myeloid-derived suppressor cell expansion in cancer patients. J Immunol 182:6562–6568

    Article  PubMed  CAS  Google Scholar 

  • Martin F, Ladoire S, Mignot G, Apetoh L, Ghiringhelli F (2010) Human FOXP3 and cancer. Oncogene 29:4121–4129

    Article  PubMed  CAS  Google Scholar 

  • Meissner M, Reichert TE, Kunkel M, Gooding W, Whiteside TL, Ferrone S, Seliger B (2005) Defects in the human leukocyte antigen class I antigen processing machinery in head and neck squamous cell carcinoma: association with clinical outcome. Clin Cancer Res 11:2552–2560

    Article  PubMed  CAS  Google Scholar 

  • Ménard C, Blay J-Y, Borg C, Michiels S, Ghiringhelli F, Robert C, Nonn C, Chaput N, Taïeb J, Delahaye NF, Flament C, Emile J-F et al (2009) Natural killer cell IFN-γ levels predict long-term survival with imatinib mesylate therapy in gastrointestinal stromal tumor-bearing patients. Cancer Res 69:3563–3569

    Article  PubMed  CAS  Google Scholar 

  • Mlecnik B, Tosolini M, Charoentong P, Kirilovsky A, Bindea G, Berger A, Camus M, Gillard M, Bruneval P, Fridman WH, Pages F, Trajanoski Z et al (2010) Biomolecular network reconstruction identifies T-cell homing factors associated with survival in colorectal cancer. Gastroenterology 138:1429–1440

    Article  PubMed  CAS  Google Scholar 

  • Montero AJ, Diaz-Montero CM, Kyriakopoulos CE, Bronte V, Mandruzzato S (2012) Myeloid-derived suppressor cells in cancer patients: a clinical perspective. J Immunother 35:107–115

    Article  PubMed  Google Scholar 

  • Moodie Z, Price L, Gouttefangeas C, Mander A, Janetzki S, Lower M, Welters MJ, Ottensmeier C, van der Burg SH, Britten CM (2010) Response definition criteria for ELISPOT assays revisited. Cancer Immunol Immunother 59:1489–1501

    Article  PubMed  CAS  Google Scholar 

  • Musolino A, Naldi N, Bortesi B, Pezzuolo D, Capelletti M, Missale G, Laccabue D, Zerbini A, Camisa R, Bisagni G, Neri TM, Ardizzoni A (2008) Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol 26:1789–1796

    Article  PubMed  CAS  Google Scholar 

  • Nagaraj S, Gabrilovich DI (2010) Myeloid-derived suppressor cells in human cancer. Cancer J 16:348–353

    Article  PubMed  CAS  Google Scholar 

  • Nakamura Y, Watchmaker P, Urban J, Sheridan B, Giermasz A, Nishimura F, Sasaki K, Cumberland R, Muthuswamy R, Mailliard RB, Larregina AT, Falo LD et al (2007) Helper function of memory CD8+ T cells: heterologous CD8+ T cells support the induction of therapeutic cancer immunity. Cancer Res 67:10012–10028

    Article  PubMed  CAS  Google Scholar 

  • Naranbhai V, Bartman P, Ndlovu D, Ramkalawon P, Ndung’u T, Wilson D, Altfeld M, Carr WH (2011) Impact of blood processing variations on natural killer cell frequency, activation, chemokine receptor expression and function. J Immunol Methods 366:28–35

    Article  PubMed  CAS  Google Scholar 

  • Nemunaitis J, Sterman D, Jablons D, Smith JW 2nd, Fox B, Maples P, Hamilton S, Borellini F, Lin A, Morali S, Hege K (2004) Granulocyte-macrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small-cell lung cancer. J Natl Cancer Inst 96:326–331

    Article  PubMed  CAS  Google Scholar 

  • Nicolette CA, Healey D, Tcherepanova I, Whelton P, Monesmith T, Coombs L, Finke LH, Whiteside T, Miesowicz F (2007) Dendritic cells for active immunotherapy: optimizing design and manufacture in order to develop commercially and clinically viable products. Vaccine 25(Suppl 2):B47–B60

    Article  PubMed  CAS  Google Scholar 

  • Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, Mintz AH, Engh JA, Bartlett DL, Brown CK, Zeh H, Holtzman MP et al (2011) Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol 29:330–336

    Article  PubMed  CAS  Google Scholar 

  • Old LJ, Chen YT (1998) New paths in human cancer serology. J Exp Med 187:1163–1167

    Article  PubMed  CAS  Google Scholar 

  • Orange JS, Ballas ZK (2006) Natural killer cells in human health and disease. Clin Immunol 118:1–10

    Article  PubMed  CAS  Google Scholar 

  • O’Rourke MG, Johnson MK, Lanagan CM, See JL, O’Connor LE, Slater GJ, Thomas D, Lopez JA, Martinez NR, Ellem KA, Schmidt CW (2007) Dendritic cell immunotherapy for stage IV melanoma. Melanoma Res 17:316–322

    Article  PubMed  CAS  Google Scholar 

  • Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, Meatchi T, Bruneval P et al (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353:2654–2666

    Article  PubMed  CAS  Google Scholar 

  • Palucka AK, Ueno H, Fay J, Banchereau J (2008) Dendritic cells: a critical player in cancer therapy? J Immunother 31:793–805

    Article  PubMed  Google Scholar 

  • Penn I (1996) Malignant melanoma in organ allograft recipients. Transplantation 61:274–278

    Article  PubMed  CAS  Google Scholar 

  • Peranzoni E, Zilio S, Marigo I, Dolcetti L, Zanovello P, Mandruzzato S, Bronte V (2010) Myeloid-derived suppressor cell heterogeneity and subset definition. Curr Opin Immunol 22:238–244

    Article  PubMed  CAS  Google Scholar 

  • Perez SA, Karamouzis MV, Skarlos DV, Ardavanis A, Sotiriadou NN, Iliopoulou EG, Salagianni ML, Orphanos G, Baxevanis CN, Rigatos G, Papamichail M (2007) CD4+ CD25+ regulatory T-cell frequency in HER-2/neu (HER)-positive and HER-negative advanced-stage breast cancer patients. Clin Cancer Res 13:2714–2721

    Article  PubMed  CAS  Google Scholar 

  • Piccioli D, Sbrana S, Melandri E, Valiante NM (2002) Contact-dependent stimulation and inhibition of dendritic cells by natural killer cells. J Exp Med 195:335–341

    Article  PubMed  CAS  Google Scholar 

  • Pinheiro SP, Hankinson SE, Tworoger SS, Rosner BA, McKolanis JR, Finn OJ, Cramer DW (2010) Anti-MUC1 antibodies and ovarian cancer risk: prospective data from the Nurses’ Health Studies. Cancer Epidemiol Biomarkers Prev 19:1595–1601

    Article  PubMed  CAS  Google Scholar 

  • Pinzon-Charry A, Ho CS, Maxwell T, McGuckin MA, Schmidt C, Furnival C, Pyke CM, Lopez JA (2007) Numerical and functional defects of blood dendritic cells in early- and late-stage breast cancer. Br J Cancer 97:1251–1259

    Article  PubMed  CAS  Google Scholar 

  • Platonova S, Cherfils-Vicini J, Damotte D, Crozet L, Vieillard V, Validire P, André P, Dieu-Nosjean M-C, Alifano M, Régnard J-F, Fridman W-H, Sautès-Fridman C et al (2011) Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res 71:5412–5422

    Article  PubMed  CAS  Google Scholar 

  • Poschke I, Mcugiakakas D, Hansson J, Masucci GV, Klessling R (2010) Immature immunosuppressive CD14+HLA-DR-/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign. Cancer Res 70:4335–4345

    Article  PubMed  CAS  Google Scholar 

  • Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, Rasalan T, Adamow M, Ritter E, Sedrak C, Jungbluth AA et al (2012) Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 366:925–931

    Article  PubMed  CAS  Google Scholar 

  • Raja SM, Metkar SS, Froelich CJ (2003) Cytotoxic granule-mediated apoptosis: unraveling the complex mechanism. Curr Opin Immunol 15:528–532

    Article  PubMed  CAS  Google Scholar 

  • Reuschenbach M, von Knebel Doeberit M, Wentzensen N (2009) A systematic review of humoral immune responses against tumor antigens. Cancer Immunol Immunother 58:1535–1544

    Article  PubMed  CAS  Google Scholar 

  • Ribas A, Glaspy JA, Lee Y, Dissette VB, Seja E, Vu HT, Tchekmedyian NS, Oseguera D, Comin-Anduix B, Wargo JA, Amarnani SN, McBride WH et al (2004) Role of dendritic cell phenotype, determinant spreading, and negative costimulatory blockade in dendritic cell-based melanoma immunotherapy. J Immunother 27:354–367

    Article  PubMed  CAS  Google Scholar 

  • Roszkowski JJ, Lyons GE, Kast WM, Yee C, Van Besien K, Nishimura MI (2005) Simultaneous generation of CD8+ and CD4+ melanoma-reactive T cells by retroviral-mediated transfer of a single T-cell receptor. Cancer Res 65:1570–1576

    Article  PubMed  CAS  Google Scholar 

  • Rubio V, Stuge TB, Singh N, Betts MR, Weber JS, Roederer M, Lee PP (2003) Ex vivo identification, isolation and analysis of tumor-cytolytic T cells. Nat Med 9:1377–1382

    Article  PubMed  CAS  Google Scholar 

  • Sakaguchi S, Miyara M, Costantino CM, Hafler DA (2010) FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10:490–500

    Article  PubMed  CAS  Google Scholar 

  • Sato E, Fujimoto J, Toyoki H, Sakaguchi H, Alam SM, Jahan I, Tamaya T (2007) Expression of IP-10 related to angiogenesis in uterine cervical cancers. Br J Cancer 96:1735–1739

    Article  PubMed  CAS  Google Scholar 

  • Schaefer C, Butterfield LH, Lee S, Kim GG, Visus C, Albers A, Kirkwood JM, Whiteside TL (2012) Function but not phenotype of melanoma peptide-specific CD8(+) T cellsT cells correlate with survival in a multiepitope peptide vaccine trial (ECOG 1696). Int J Cancer 131:874–884

    Article  PubMed  CAS  Google Scholar 

  • Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, Gailani F, Riley L, Conlon K, Pockaj B, Kendra KL, White RL et al (2011) gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med 364:2119–2127

    Article  PubMed  CAS  Google Scholar 

  • Seliger B, Abken H, Ferrone S (2003) HLA-G and MIC expression in tumors and their role in anti-tumor immunity. Trends Immunol 24:82–87

    Article  PubMed  CAS  Google Scholar 

  • Shafer-Weaver K, Sayers T, Strobl S, Derby E, Ulderich T, Baseler M, Malyguine A (2003) The Granzyme B ELISPOT assay: an alternative to the 51Cr-release assay for monitoring cell-mediated cytotoxicity. J Transl Med 1:14

    Article  PubMed  Google Scholar 

  • Sheikh NA, Jones LA (2008) CD54 is a surrogate marker of antigen presenting cell activation. Cancer Immunol Immunother 57:1381–1390

    Article  PubMed  CAS  Google Scholar 

  • Sheikh NA, Petrylak D, Kantoff PW, Dela Rosa C, Stewart FP, Kuan LY, Whitmore JB, Trager JB, Poehlein CH, Frohlich MW, Urdal DL (2012) Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer. Cancer Immunol Immunother

    Google Scholar 

  • Slingluff CL Jr, Petroni GR, Yamshchikov GV, Hibbitts S, Grosh WW, Chianese-Bullock KA, Bissonette EA, Barnd DL, Deacon DH, Patterson JW, Parekh J, Neese PY et al (2004) Immunologic and clinical outcomes of vaccination with a multiepitope melanoma peptide vaccine plus low-dose interleukin-2 administered either concurrently or on a delayed schedule. J Clin Oncol 22:4474–4485

    Article  PubMed  CAS  Google Scholar 

  • Slingluff CL Jr, Petroni GR, Chianese-Bullock KA, Smolkin ME, Hibbitts S, Murphy C, Johansen N, Grosh WW, Yamshchikov GV, Neese PY, Patterson JW, Fink R et al (2007) Immunologic and clinical outcomes of a randomized phase II trial of two multipeptide vaccines for melanoma in the adjuvant setting. Clin Cancer Res 13:6386–6395

    Article  PubMed  CAS  Google Scholar 

  • Slingluff CL Jr, Petroni GR, Olson W, Czarkowski A, Grosh WW, Smolkin M, Chianese-Bullock KA, Neese PY, Deacon DH, Nail C, Merrill P, Fink R et al (2008) Helper T-cell responses and clinical activity of a melanoma vaccine with multiple peptides from MAGE and melanocytic differentiation antigens. J Clin Oncol 26:4973–4980

    Article  PubMed  Google Scholar 

  • Spaggiari GM, Carosio R, Pende D, Marcenaro S, Rivera P, Zocchi MR, Moretta L, Poggi A (2001) NK cell mediated lysis of autologous antigen presenting cells is triggered by the engagement of the phosphatidylinositol 3-kinase upon ligation of the natural cytotoxicity receptors NKp30a nad NKp46. Eur J Immunol 3:1656–1665

    Article  Google Scholar 

  • Surman D, Dudley M, Overwijk W, Restifo N (2000) Cutting edge: CD4+ T cell control of CD8+ T cell reactivity to a model tumor antigen. J Immunol 164:562–565

    PubMed  CAS  Google Scholar 

  • Tahara H, Sato M, Thurin M, Wang E, Butterfield LH, Disis ML, Fox BA, Lee PP, Khleif SN, Wigginton JM, Ambs S, Akutsu Y et al (2009) Emerging concepts in biomarker discovery; the US-Japan workshop on immunological molecular markers in oncology. J Transl Med 7:45

    Article  PubMed  CAS  Google Scholar 

  • Tatsumi T, Kierstead LS, Ranieri E, Gesualdo L, Schena FP, Finke JH, Bukowski RM, Mueller-Berghaus J, Kirkwood JM, Kwok WW, Storkus WJ (2002) Disease-associated bias in T helper type 1 (Th1)/Th2 CD4(+) T cell responses against MAGE-6 in HLA-DRB10401(+) patients with renal cell carcinoma or melanoma. J Exp Med 196:619–628

    Article  PubMed  CAS  Google Scholar 

  • Taylor C, Hershman D, Shah N, Suciu-Foca N, Petrylak DP, Taub R, Vahdat L, Cheng B, Pegram M, Knutson KL, Clynes R (2007) Augmented HER-2 specific immunity during treatment with trastuzumab and chemotherapy. Clin Cancer Res 13:5133–5143

    Article  PubMed  CAS  Google Scholar 

  • Toedter G, Hayden K, Wagner C, Brodmerkel C (2008) Simultaneous detection of eight analytes in human serum by two commercially available platforms for multiplex cytokine analysis. Clin Vaccine Immunol 15:42–48

    Article  PubMed  CAS  Google Scholar 

  • Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454

    Article  PubMed  CAS  Google Scholar 

  • Uccellini L, De Giorgi V, Zhao Y, Tumaini B, Erdenebileg N, Dudley ME, Tomei S, Bedognetti D, Ascierto ML, Liu Q, Simon R, Kottyan L et al (2012) IRF5 gene polymorphisms in melanoma. J Transl Med 10:170

    Article  PubMed  CAS  Google Scholar 

  • Ugurel S, Schrama D, Keller G, Schadendorf D, Brocker EB, Houben R, Zapatka M, Fink W, Kaufman HL, Becker JC (2008) Impact of the CCR5 gene polymorphism on the survival of metastatic melanoma patients receiving immunotherapy. Cancer Immunol Immunother 57:685–691

    Article  PubMed  CAS  Google Scholar 

  • van Cruijsen H, van der Veldt AA, Vroling L, Oosterhoff D, Broxterman HJ, Scheper RJ, Giaccone G, Haanen JB, van den Eertwegh AJ, Boven E, Hoekman K, de Gruijl TD (2008) Sunitinib-induced myeloid lineage redistribution in renal cell cancer patients: CD1c+ dendritic cell frequency predicts progression-free survival. Clin Cancer Res 14:5884–5892

    Article  PubMed  CAS  Google Scholar 

  • van Tendeloo VF, van de Velde A, van Driessche A, Cools N, Anguille S, Ladell K, Gostick E, Vermeulen K, Pieters K, Nijs G, Stein B, Smits EL et al (2010) Induction of complete and molecular remissions in acute myeloid leukemia by Wilms’ tumor 1 antigen-targeted dendritic cell vaccination. Proc Natl Acad Sci U S A 107:13824–13829

    Article  PubMed  Google Scholar 

  • Vergati M, Cereda V, Madan RA, Gulley JL, Huen NY, Rogers CJ, Hance KW, Arlen PM, Schlom J, Tsang KY (2011) Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre- versus post-vaccination. Cancer Immunol Immunother 60:197–206

    Article  PubMed  Google Scholar 

  • Vivier E, Ugolini S, Blaise D, Chabannon C, Brossay L (2012) Targeting natural killer cells and natural killer T cells in cancer. Nat Rev Immunol 12:239–252

    Article  PubMed  CAS  Google Scholar 

  • von Mensdorff-Pouilly S, Verstraeten AA, Kenemans P, Snijdewint FG, Kok A, van Kamp GJ, Paul MA, Van Diest PJ, Meijer S, Hilgers J (2000) Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin. J Clin Oncol 18:574–583

    Google Scholar 

  • Vujanovic NL (2001) Role of TNF family ligands in antitumor activity of natural killer cells. Internat Rev Immunol 20:415–435

    Article  CAS  Google Scholar 

  • Vujanovic L, Szymkowski DE, Vujanovic NL, Butterfield LH (2010) Virally-infected and cytokine-matured human dendritic cells activate natural killer cells via cooperative activity of plasma membrane-bound TNF and IL-15. Blood 116:575–583

    Article  PubMed  CAS  Google Scholar 

  • Wakabayashi O, Yamazaki K, Oizumi S, Hommura F, Kinoshita I, Ogura S, Dosaka-Akita H, Nishimura M (2003) CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers. Cancer Sci 94:1003–1009

    Article  PubMed  CAS  Google Scholar 

  • Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C, Staehler M, Brugger W, Dietrich PY, Mendrzyk R, Hilf N, Schoor O et al (2012) Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med

    Google Scholar 

  • Wang E, Uccellini L, Marincola FM (2012a) A genetic inference on cancer immune responsiveness. Oncoimmunology 1:520–525

    Article  PubMed  Google Scholar 

  • Wang E, Zhao Y, Monaco A, Uccellini L, Kirkwood JM, Spyropoulou-Vlachou M, Panelli MC, Marincola FM, Gogas H (2012b) A multi-factorial genetic model for prognostic assessment of high risk melanoma patients receiving adjuvant interferon. PLoS ONE 7:e40805

    Article  PubMed  CAS  Google Scholar 

  • Weide B, Zelba H, Derhovanessian E, Pflugfelder A, Eigentler TK, di Giacomo AM, Maio M, Aarntzen EH, de Vries IJ, Sucker A, Schadendorf D, Buttner P et al (2012) Functional T cells targeting NY-ESO-1 or Melan-A are predictive for survival of patients with distant melanoma metastasis. J Clin Oncol 30:1835–1841

    Article  PubMed  CAS  Google Scholar 

  • Weiner HL (2001) Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol Rev 182:207–214

    Article  PubMed  CAS  Google Scholar 

  • Welters MJ, Kenter GG, de Vos van Steenwijk PJ, Lowik MJ, Berends-van der Meer DM, Essahsah F, Stynenbosch LF, Vloon AP, Ramwadhdoebe TH, Piersma SJ, van der Hulst JM, Valentijn AR et al. (2010) Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses. Proc Natl Acad Sci U S A 107:11895–11899

    Google Scholar 

  • Westwell-Roper C, Dai DL, Soukhatcheva G, Potter KJ, van Rooijen N, Ehses JA, Verchere CB (2011) IL-1 blockade attenuates islet amyloid polypeptide-induced proinflammatory cytokine release and pancreatic islet graft dysfunction. J Immunol 187:2755–2765

    Article  PubMed  CAS  Google Scholar 

  • Whiteside TL, Schuler P (2012) Schilling B. Induced and natural regulatory T cells in human cancer, Expert Opin Biol Ther

    Google Scholar 

  • Whiteside TL, Zhao Y, Tsukishiro T, Elder EM, Gooding W, Baar J (2003) Enzyme-linked immunospot, cytokine flow cytometry, and tetramers in the detection of T-cell responses to a dendritic cell-based multipeptide vaccine in patients with melanoma. Clin Cancer Res 9:641–649

    PubMed  CAS  Google Scholar 

  • Wiegering V, Eyrich M, Rutkowski S, Wolfl M, Schlegel PG, Winkler B (2011) TH1 predominance is associated with improved survival in pediatric medulloblastoma patients. Cancer Immunol Immunother 60:693–703

    Article  PubMed  CAS  Google Scholar 

  • Wierecky J, Muller MR, Wirths S, Halder-Oehler E, Dorfel D, Schmidt SM, Hantschel M, Brugger W, Schroder S, Horger MS, Kanz L, Brossart P (2006) Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients. Cancer Res 66:5910–5918

    Article  PubMed  CAS  Google Scholar 

  • Wiesel M, Oxenius A (2012) From crucial to negligible: functional CD8+ T-cell responses and their dependence on CD4+ T-cell help. Eur J Immunol 42:1080–1088

    Article  PubMed  CAS  Google Scholar 

  • Wolchok JD, Neyns B, Linette G, Negrier S, Lutzky J, Thomas L, Waterfield W, Schadendorf D, Smylie M, Guthrie T Jr, Grob JJ, Chesney J et al (2010) Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol 11:155–164

    Article  PubMed  CAS  Google Scholar 

  • Xu J, Chakrabarti AK, Tan JA, Ge L, Gambotto A, Vujanovic NL (2007) Essential role of the TNF-TNFR2 cognate interaction in mouse dendritic cell-natural killer cell cross-talk. Blood 109:3333–3341

    Article  PubMed  CAS  Google Scholar 

  • Yoshida N, Abe H, Ohkuri T, Wakita D, Sato M, Noguchi D, Miyamoto M, Morikawa T, Kondo S, Ikeda H, Nishimura T (2006) Expression of the MAGE-A4 and NY-ESO-1 cancer-testis antigens and T cell infiltration in non-small cell lung carcinoma and their prognostic significance. Int J Oncol 28:1089–1098

    PubMed  CAS  Google Scholar 

  • Youn JI, Gabrilovich DI (2010) The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity. Eur J Immunol 40:2969–2975

    Article  PubMed  CAS  Google Scholar 

  • Yuan J, Adamow M, Ginsberg BA, Rasalan TS, Ritter E, Gallardo HF, Xu Y, Pogoriler E, Terzulli SL, Kuk D, Panageas KS, Ritter G et al (2011) Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. Proc Natl Acad Sci U S A 108:16723–16728

    Article  PubMed  CAS  Google Scholar 

  • Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, McDermott D, Quiceno D, Youmans A, O’Neill A, Mier J, Ochoa AC (2005) Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res 65:3044–3048

    PubMed  CAS  Google Scholar 

  • Zerbini A, Pilli M, Penna A, Pelosi G, Schianchi C, Molinari A, Schivazappa S, Zibera C, Fagnoni FF, Ferrari C, Missale G (2006) Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses. Cancer Res 66:1139–1146

    Article  PubMed  CAS  Google Scholar 

  • Zhang W, Gordon M, Schultheis AM, Yang DY, Nagashima F, Azuma M, Chang HM, Borucka E, Lurje G, Sherrod AE, Iqbal S, Groshen S et al (2007) FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. J Clin Oncol 25:3712–3718

    Article  PubMed  CAS  Google Scholar 

  • Zhang JP, Yan J, Xu J, Pang XH, Chen MS, Li L, Wu C, Li SP, Zheng L (2009) Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol 50:980–989

    Article  PubMed  CAS  Google Scholar 

  • Zitvogel L, Kepp O, Kroemer G (2011) Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat Rev Clin Oncol 8:151–160

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Hillman Cancer Center, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5117 Centre Avenue, Suite 1.27, Pittsburgh, PA, 15213, USA

    Lisa H. Butterfield, Lazar Vujanovic & Angela D. Pardee

  2. Departments of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Lisa H. Butterfield, Lazar Vujanovic & Angela D. Pardee

  3. Departments of Immunology, University of Pittsburgh, Pittsburgh, PA, USA

    Lisa H. Butterfield

  4. Departments of Surgery, University of Pittsburgh, Pittsburgh, PA, USA

    Lisa H. Butterfield

Authors
  1. Lisa H. Butterfield
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  2. Lazar Vujanovic
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  3. Angela D. Pardee
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Corresponding author

Correspondence to Lisa H. Butterfield .

Editor information

Editors and Affiliations

  1. Department of Pathology, University of Pittsburgh Medical Center, 3550 Terrace Street Scaife Hal, Pittsburgh, 15213, Pennsylvania, USA

    Michael R. Shurin

  2. , Clinical Cooperation Unit Dermato-Oncolo, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany

    Viktor Umansky

  3. , SAIC-Frederick, Inc., National Cancer Institute at Frederick, Post Office B, Frederick, 21702, Maryland, USA

    Anatoli Malyguine

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Butterfield, L.H., Vujanovic, L., Pardee, A.D. (2013). Approaches to Immunologic Monitoring of Clinical Trials. In: Shurin, M., Umansky, V., Malyguine, A. (eds) The Tumor Immunoenvironment. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6217-6_29

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