Advertisement

Innate and Adaptive Immune Responses to Cancer

  • Matthew P. Rausch
  • Karen Taraszka HastingsEmail author
Chapter

Abstract

Together, innate and adaptive immune responses are capable of recognizing and destroying cancer. Under selective pressure from the immune response, tumors evolve to escape immune-mediated destruction. Natural killer cells and gamma-delta T cells recognize and kill tumor cells. Cancer patients generate CD4+ and CD8+ T lymphocytes, which are found to be infiltrating tumors and in the peripheral blood. Brisk tumor-infiltrating lymphocytes in primary melanoma portend a survival advantage. Furthermore, the presence of tumor-infiltrating lymphocytes is associated with improved clinical responses to certain types of immunotherapy. The success of immune checkpoint inhibitors in the treatment of a broad range of cancers underscores the critical role of T cells in cancer destruction. The importance of the immune system in preventing cancer is reflected in the increased frequency of malignancies in immunosuppressed and immunodeficient patients. Furthermore, vaccination against human papillomavirus and hepatitis B virus protects against the development of cancers associated with these viruses.

Keywords

Natural killer cell Dendritic cell Macrophage Myeloid-derived suppressor cell Tumor antigen Cytokines T lymphocyte B lymphocyte Human papillomavirus Hepatitis B virus Immune checkpoint Cancer 

References

  1. Algarra I, Garcia-Lora A, Cabrera T, Ruiz-Cabello F, Garrido F (2004) The selection of tumor variants with altered expression of classical and nonclassical MHC class I molecules: implications for tumor immune escape. Cancer Immunol Immunother 53(10):904–910PubMedCrossRefPubMedCentralGoogle Scholar
  2. Amsen D, Spilianakis CG, Flavell RA (2009) How are T(H)1 and T(H)2 effector cells made? Curr Opin Immunol 21(2):153–160.  https://doi.org/10.1016/j.coi.2009.03.010CrossRefPubMedPubMedCentralGoogle Scholar
  3. Anderson KS, Wong J, Vitonis A, Crum CP, Sluss PM, Labaer J et al (2010) p53 autoantibodies as potential detection and prognostic biomarkers in serous ovarian cancer. Cancer Epidemiol Biomark Prev 19(3):859–868.  https://doi.org/10.1158/1055-9965.EPI-09-0880CrossRefGoogle Scholar
  4. Anderson KS, Sibani S, Wallstrom G, Qiu J, Mendoza EA, Raphael J et al (2011a) Protein microarray signature of autoantibody biomarkers for the early detection of breast cancer. J Proteome Res 10(1):85–96.  https://doi.org/10.1021/pr100686bCrossRefPubMedPubMedCentralGoogle Scholar
  5. Anderson KS, Wong J, D'Souza G, Riemer AB, Lorch J, Haddad R et al (2011b) Serum antibodies to the HPV16 proteome as biomarkers for head and neck cancer. Br J Cancer 104(12):1896–1905.  https://doi.org/10.1038/bjc.2011.171CrossRefPubMedPubMedCentralGoogle Scholar
  6. Arens R, Schoenberger SP (2010) Plasticity in programming of effector and memory CD8 T-cell formation. Immunol Rev 235(1):190–205.  https://doi.org/10.1111/j.0105-2896.2010.00899.xCrossRefPubMedPubMedCentralGoogle Scholar
  7. Ascierto PA, Napolitano M, Celentano E, Simeone E, Gentilcore G, Daponte A et al (2010) Regulatory T cell frequency in patients with melanoma with different disease stage and course, and modulating effects of high-dose interferon-alpha 2b treatment. J Transl Med 8:76.  https://doi.org/10.1186/1479-5876-8-76CrossRefPubMedPubMedCentralGoogle Scholar
  8. Azimi F, Scolyer RA, Rumcheva P, Moncrieff M, Murali R, McCarthy SW et al (2012) Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol Off J Am Soc Clin Oncol 30(21):2678–2683.  https://doi.org/10.1200/JCO.2011.37.8539CrossRefGoogle Scholar
  9. Azuma K, Shichijo S, Maeda Y, Nakatsura T, Nonaka Y, Fujii T et al (2003) Mutated p53 gene encodes a nonmutated epitope recognized by HLA-B*4601-restricted and tumor cell-reactive CTLs at tumor site. Cancer Res 63(4):854–858PubMedPubMedCentralGoogle Scholar
  10. Baitsch L, Baumgaertner P, Devevre E, Raghav SK, Legat A, Barba L et al (2011) Exhaustion of tumor-specific CD8(+) T cells in metastases from melanoma patients. J Clin Invest 121(6):2350–2360.  https://doi.org/10.1172/JCI46102CrossRefPubMedPubMedCentralGoogle Scholar
  11. Balachandran VP, Luksza M, Zhao JN, Makarov V, Moral JA, Remark R et al (2017) Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature 551(7681):512–516.  https://doi.org/10.1038/nature24462CrossRefPubMedPubMedCentralGoogle Scholar
  12. Baldus SE, Engelmann K, Hanisch FG (2004) MUC1 and the MUCs: a family of human mucins with impact in cancer biology. Crit Rev Clin Lab Sci 41(2):189–231PubMedCrossRefPubMedCentralGoogle Scholar
  13. Balkwill F (2009) Tumour necrosis factor and cancer. Nat Rev Cancer 9(5):361–371.  https://doi.org/10.1038/nrc2628CrossRefPubMedPubMedCentralGoogle Scholar
  14. Baurain JF, Colau D, van Baren N, Landry C, Martelange V, Vikkula M et al (2000) High frequency of autologous anti-melanoma CTL directed against an antigen generated by a point mutation in a new helicase gene. J Immunol 164(11):6057–6066PubMedCrossRefPubMedCentralGoogle Scholar
  15. Begley M, Gahan CG, Kollas AK, Hintz M, Hill C, Jomaa H et al (2004) The interplay between classical and alternative isoprenoid biosynthesis controls gammadelta T cell bioactivity of Listeria monocytogenes. FEBS Lett 561(1–3):99–104PubMedCrossRefPubMedCentralGoogle Scholar
  16. Belicha-Villanueva A, Golding M, McEvoy S, Sarvaiya N, Cresswell P, Gollnick SO et al (2010) Identification of an alternate splice form of tapasin in human melanoma. Hum Immunol 71(10):1018–1026.  https://doi.org/10.1016/j.humimm.2010.05.019CrossRefPubMedPubMedCentralGoogle Scholar
  17. Beyer M, Kochanek M, Darabi K, Popov A, Jensen M, Endl E et al (2005) Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood 106(6):2018–2025PubMedCrossRefPubMedCentralGoogle Scholar
  18. Birkeland SA, Storm HH, Lamm LU, Barlow L, Blohme I, Forsberg B et al (1995) Cancer risk after renal transplantation in the Nordic countries, 1964–1986. Int J Cancer 60(2):183–189PubMedCrossRefPubMedCentralGoogle Scholar
  19. Bonneville M, Scotet E (2006) Human Vgamma9Vdelta2 T cells: promising new leads for immunotherapy of infections and tumors. Curr Opin Immunol 18(5):539–546PubMedCrossRefPubMedCentralGoogle Scholar
  20. Bosch GJ, Joosten AM, Kessler JH, Melief CJ, Leeksma OC (1996) Recognition of BCR-ABL positive leukemic blasts by human CD4+ T cells elicited by primary in vitro immunization with a BCR-ABL breakpoint peptide. Blood 88(9):3522–3527PubMedPubMedCentralGoogle Scholar
  21. Bourdon JC (2007) p53 and its isoforms in cancer. Br J Cancer 97(3):277–282PubMedPubMedCentralCrossRefGoogle Scholar
  22. Brandes M, Willimann K, Moser B (2005) Professional antigen-presentation function by human gammadelta T cells. Science 309(5732):264–268PubMedCrossRefPubMedCentralGoogle Scholar
  23. Brandt CS, Baratin M, Yi EC, Kennedy J, Gao Z, Fox B et al (2009) The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans. J Exp Med 206(7):1495–1503.  https://doi.org/10.1084/jem.20090681CrossRefPubMedPubMedCentralGoogle Scholar
  24. Brunet JF, Denizot F, Luciani MF, Roux-Dosseto M, Suzan M, Mattei MG et al (1987) A new member of the immunoglobulin superfamily—CTLA-4. Nature 328(6127):267–270.  https://doi.org/10.1038/328267a0CrossRefPubMedPubMedCentralGoogle Scholar
  25. Bryant KL, Mancias JD, Kimmelman AC, Der CJ (2014) KRAS: feeding pancreatic cancer proliferation. Trends Biochem Sci 39(2):91–100.  https://doi.org/10.1016/j.tibs.2013.12.004CrossRefPubMedPubMedCentralGoogle Scholar
  26. Bukowski JF, Morita CT, Tanaka Y, Bloom BR, Brenner MB, Band H (1995) V gamma 2V delta 2 TCR-dependent recognition of non-peptide antigens and Daudi cells analyzed by TCR gene transfer. J Immunol 154(3):998–1006PubMedPubMedCentralGoogle Scholar
  27. Burnet FM (1957) Cancer: a biological approach. Br Med J 1:841–847PubMedPubMedCentralCrossRefGoogle Scholar
  28. Burton AL, Roach BA, Mays MP, Chen AF, Ginter BA, Vierling AM et al (2011) Prognostic significance of tumor infiltrating lymphocytes in melanoma. Am Surg 77(2):188–192PubMedPubMedCentralGoogle Scholar
  29. Byrne WL, Mills KH, Lederer JA, O'Sullivan GC (2011) Targeting regulatory T cells in cancer. Cancer Res 71(22):6915–6920.  https://doi.org/10.1158/0008-5472.CAN-11-1156CrossRefPubMedPubMedCentralGoogle Scholar
  30. Cassard L, Cohen-Solal J, Camilleri-Broet S, Fournier E, Fridman WH, Sautes-Fridman C (2006) Fc gamma receptors and cancer. Springer Semin Immunopathol 28(4):321–328PubMedCrossRefPubMedCentralGoogle Scholar
  31. Chang MH, You SL, Chen CJ, Liu CJ, Lai MW, Wu TC et al (2016) Long-term effects of hepatitis B immunization of infants in preventing liver cancer. Gastroenterology 151(3):472–80.e1.  https://doi.org/10.1053/j.gastro.2016.05.048CrossRefPubMedPubMedCentralGoogle Scholar
  32. Chapman C, Murray A, Chakrabarti J, Thorpe A, Woolston C, Sahin U et al (2007) Autoantibodies in breast cancer: their use as an aid to early diagnosis. Ann Oncol 18(5):868–873.  https://doi.org/10.1093/annonc/mdm007CrossRefPubMedPubMedCentralGoogle Scholar
  33. Chapon M, Randriamampita C, Maubec E, Badoual C, Fouquet S, Wang SF et al (2011) Progressive upregulation of PD-1 in primary and metastatic melanomas associated with blunted TCR signaling in infiltrating T lymphocytes. J Invest Dermatol 131(6):1300–1307.  https://doi.org/10.1038/jid.2011.30CrossRefPubMedPubMedCentralGoogle Scholar
  34. Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL (2004) SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol 173(2):945–954PubMedCrossRefPubMedCentralGoogle Scholar
  35. Chen X, Wan J, Liu J, Xie W, Diao X, Xu J et al (2010) Increased IL-17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients. Lung Cancer 69(3):348–354.  https://doi.org/10.1016/j.lungcan.2009.11.013CrossRefPubMedPubMedCentralGoogle Scholar
  36. Chiari R, Foury F, De Plaen E, Baurain JF, Thonnard J, Coulie PG (1999) Two antigens recognized by autologous cytolytic T lymphocytes on a melanoma result from a single point mutation in an essential housekeeping gene. Cancer Res 59(22):5785–5792PubMedPubMedCentralGoogle Scholar
  37. Clark WH Jr, Elder DE, Guerry D, Braitman LE, Trock BJ, Schultz D et al (1989) Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst 81(24):1893–1904PubMedCrossRefPubMedCentralGoogle Scholar
  38. Clemente CG, Mihm MC Jr, 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(7):1303–1310.  https://doi.org/10.1002/(SICI)1097-0142(19960401)77:7<1303::AID-CNCR12>3.0.CO;2-5CrossRefPubMedPubMedCentralGoogle Scholar
  39. Corvaisier M, Moreau-Aubry A, Diez E, Bennouna J, Mosnier JF, Scotet E et al (2005) V gamma 9V delta 2 T cell response to colon carcinoma cells. J Immunol 175(8):5481–5488PubMedCrossRefPubMedCentralGoogle Scholar
  40. Coulie PG, Lehmann F, Lethe B, Herman J, Lurquin C, Andrawiss M et al (1995) A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma. Proc Natl Acad Sci U S A 92(17):7976–7980PubMedPubMedCentralCrossRefGoogle Scholar
  41. Cresswell P, Ackerman AL, Giodini A, Peaper DR, Wearsch PA (2005) Mechanisms of MHC class I-restricted antigen processing and cross-presentation. Immunol Rev 207:145–157PubMedCrossRefPubMedCentralGoogle Scholar
  42. Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P et al (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9(5):562–567PubMedCrossRefPubMedCentralGoogle Scholar
  43. Das H, Groh V, Kuijl C, Sugita M, Morita CT, Spies T et al (2001) MICA engagement by human Vgamma2Vdelta2 T cells enhances their antigen-dependent effector function. Immunity 15(1):83–93PubMedCrossRefPubMedCentralGoogle Scholar
  44. Del Vecchio M, Bajetta E, Canova S, Lotze MT, Wesa A, Parmiani G et al (2007) Interleukin-12: biological properties and clinical application. Clin Cancer Res 13(16):4677–4685PubMedCrossRefPubMedCentralGoogle Scholar
  45. van den Broek ME, Kagi D, Ossendorp F, Toes R, Vamvakas S, Lutz WK et al (1996) Decreased tumor surveillance in perforin-deficient mice. J Exp Med 184(5):1781–1790PubMedCrossRefPubMedCentralGoogle Scholar
  46. Desmetz C, Bascoul-Mollevi C, Rochaix P, Lamy PJ, Kramar A, Rouanet P et al (2009) Identification of a new panel of serum autoantibodies associated with the presence of in situ carcinoma of the breast in younger women. Clin Cancer Res 15(14):4733–4741.  https://doi.org/10.1158/1078-0432.CCR-08-3307CrossRefPubMedPubMedCentralGoogle Scholar
  47. 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(1):49–59.  https://doi.org/10.1007/s00262-008-0523-4CrossRefPubMedPubMedCentralGoogle Scholar
  48. Dighe AS, Richards E, Old LJ, Schreiber RD (1994) Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1(6):447–456PubMedCrossRefPubMedCentralGoogle Scholar
  49. Dong H, Zhu G, Tamada K, Chen L (1999) B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 5(12):1365–1369.  https://doi.org/10.1038/70932CrossRefPubMedPubMedCentralGoogle Scholar
  50. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB et al (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8(8):793–800.  https://doi.org/10.1038/nm730CrossRefPubMedPubMedCentralGoogle Scholar
  51. Durrant LG, Noble P, Spendlove I (2012) Immunology in the clinic review series; focus on cancer: glycolipids as targets for tumour immunotherapy. Clin Exp Immunol. 167(2):206–215.  https://doi.org/10.1111/j.1365-2249.2011.04516.xCrossRefPubMedPubMedCentralGoogle Scholar
  52. Efremova M, Finotello F, Rieder D, Trajanoski Z (2017) Neoantigens generated by individual mutations and their role in cancer immunity and immunotherapy. Front Immunol 8:1679.  https://doi.org/10.3389/fimmu.2017.01679CrossRefPubMedPubMedCentralGoogle Scholar
  53. Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H et al (2016) Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med 375(19):1845–1855.  https://doi.org/10.1056/NEJMoa1611299CrossRefPubMedPubMedCentralGoogle Scholar
  54. Eppihimer MJ, Gunn J, Freeman GJ, Greenfield EA, Chernova T, Erickson J et al (2002) Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells. Microcirculation 9(2):133–145.  https://doi.org/10.1038/sj/mn/7800123CrossRefPubMedPubMedCentralGoogle Scholar
  55. Erfani N, Mehrabadi SM, Ghayumi MA, Haghshenas MR, Mojtahedi Z, Ghaderi A et al (2012) Increase of regulatory T cells in metastatic stage and CTLA-4 over expression in lymphocytes of patients with non-small cell lung cancer (NSCLC). Lung Cancer 77(2):306–311.  https://doi.org/10.1016/j.lungcan.2012.04.011CrossRefPubMedPubMedCentralGoogle Scholar
  56. Finkelstein SE, Carey T, Fricke I, Yu D, Goetz D, Gratz M 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(8):817–827.  https://doi.org/10.1097/CJI.0b013e3181ecccadCrossRefPubMedPubMedCentralGoogle Scholar
  57. Fisch P, Malkovsky M, Kovats S, Sturm E, Braakman E, Klein BS et al (1990) Recognition by human V gamma 9/V delta 2 T cells of a GroEL homolog on Daudi Burkitt’s lymphoma cells. Science 250(4985):1269–1273PubMedCrossRefPubMedCentralGoogle Scholar
  58. Fisch P, Meuer E, Pende D, Rothenfusser S, Viale O, Kock S et al (1997) Control of B cell lymphoma recognition via natural killer inhibitory receptors implies a role for human Vgamma9/Vdelta2 T cells in tumor immunity. Eur J Immunol 27(12):3368–3379PubMedCrossRefPubMedCentralGoogle Scholar
  59. Fisk B, Blevins TL, Wharton JT, Ioannides CG (1995) Identification of an immunodominant peptide of HER-2/neu protooncogene recognized by ovarian tumor-specific cytotoxic T lymphocyte lines. J Exp Med 181(6):2109–2117PubMedCrossRefPubMedCentralGoogle Scholar
  60. Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limon P (2010) The polarization of immune cells in the tumour environment by TGFbeta. Nat Rev Immunol 10(8):554–567.  https://doi.org/10.1038/nri2808CrossRefPubMedPubMedCentralGoogle Scholar
  61. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H et al (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192(7):1027–1034PubMedPubMedCentralCrossRefGoogle Scholar
  62. Fritz JM, Tennis MA, Orlicky DJ, Lin H, Ju C, Redente EF et al (2014) Depletion of tumor-associated macrophages slows the growth of chemically induced mouse lung adenocarcinomas. Front Immunol 5:587.  https://doi.org/10.3389/fimmu.2014.00587CrossRefPubMedPubMedCentralGoogle Scholar
  63. Fujii H, Arakawa A, Kitoh A, Miyara M, Kato M, Kore-eda S et al (2011) Perturbations of both nonregulatory and regulatory FOXP3+ T cells in patients with malignant melanoma. Br J Dermatol 164(5):1052–1060.  https://doi.org/10.1111/j.1365-2133.2010.10199.xCrossRefPubMedPubMedCentralGoogle Scholar
  64. Fujita H, Senju S, Yokomizo H, Saya H, Ogawa M, Matsushita S et al (1998) Evidence that HLA class II-restricted human CD4+ T cells specific to p53 self peptides respond to p53 proteins of both wild and mutant forms. Eur J Immunol 28(1):305–316PubMedCrossRefPubMedCentralGoogle Scholar
  65. 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(10):1419–1430.  https://doi.org/10.1007/s00262-011-1028-0CrossRefPubMedPubMedCentralGoogle Scholar
  66. Garcia-Hernandez Mde L, Hamada H, Reome JB, Misra SK, Tighe MP, Dutton RW (2010) Adoptive transfer of tumor-specific Tc17 effector T cells controls the growth of B16 melanoma in mice. J Immunol 184(8):4215–4227.  https://doi.org/10.4049/jimmunol.0902995CrossRefPubMedPubMedCentralGoogle Scholar
  67. Girardi M, Oppenheim DE, Steele CR, Lewis JM, Glusac E, Filler R et al (2001) Regulation of cutaneous malignancy by gammadelta T cells. Science 294(5542):605–609PubMedCrossRefPubMedCentralGoogle Scholar
  68. Gjertsen MK, Bjorheim J, Saeterdal I, Myklebust J, Gaudernack G (1997) Cytotoxic CD4+ and CD8+ T lymphocytes, generated by mutant p21-ras (12Val) peptide vaccination of a patient, recognize 12Val-dependent nested epitopes present within the vaccine peptide and kill autologous tumour cells carrying this mutation. Int J Cancer 72(5):784–790PubMedCrossRefPubMedCentralGoogle Scholar
  69. Gober HJ, Kistowska M, Angman L, Jeno P, Mori L, De Libero G (2003) Human T cell receptor gammadelta cells recognize endogenous mevalonate metabolites in tumor cells. J Exp Med 197(2):163–168PubMedPubMedCentralCrossRefGoogle Scholar
  70. Goh G, Walradt T, Markarov V, Blom A, Riaz N, Doumani R et al (2016) Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy. Oncotarget 7(3):3403–3415.  https://doi.org/10.18632/oncotarget.6494CrossRefPubMedPubMedCentralGoogle Scholar
  71. Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein KH, Spies T (1999) Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proc Natl Acad Sci U S A 96(12):6879–6884PubMedPubMedCentralCrossRefGoogle Scholar
  72. Gros A, Robbins PF, Yao X, Li YF, Turcotte S, Tran E et al (2014) PD-1 identifies the patient-specific CD8(+) tumor-reactive repertoire infiltrating human tumors. J Clin Invest 124(5):2246–2259.  https://doi.org/10.1172/JCI73639CrossRefPubMedPubMedCentralGoogle Scholar
  73. Group FIS (2007) Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med 356(19):1915–1927.  https://doi.org/10.1056/NEJMoa061741CrossRefGoogle Scholar
  74. Guo BL, Liu Z, Aldrich WA, Lopez RD (2005) Innate anti-breast cancer immunity of apoptosis-resistant human gammadelta-T cells. Breast Cancer Res Treat 93(2):169–175PubMedCrossRefPubMedCentralGoogle Scholar
  75. Guo Y, Luan L, Patil NK, Sherwood ER (2017) Immunobiology of the IL-15/IL-15Ralpha complex as an antitumor and antiviral agent. Cytokine Growth Factor Rev 38:10–21.  https://doi.org/10.1016/j.cytogfr.2017.08.002CrossRefPubMedPubMedCentralGoogle Scholar
  76. Hammes LS, Tekmal RR, Naud P, Edelweiss MI, Kirma N, Valente PT et al (2007) Macrophages, inflammation and risk of cervical intraepithelial neoplasia (CIN) progression--clinicopathological correlation. Gynecol Oncol 105(1):157–165.  https://doi.org/10.1016/j.ygyno.2006.11.023CrossRefPubMedPubMedCentralGoogle Scholar
  77. Haque MA, Li P, Jackson SK, Zarour HM, Hawes JW, Phan UT et al (2002) Absence of gamma-interferon-inducible lysosomal thiol reductase in melanomas disrupts T cell recognition of select immunodominant epitopes. J Exp Med 195(10):1267–1277PubMedPubMedCentralCrossRefGoogle Scholar
  78. Hastings KT, Cresswell P (2011) Disulfide reduction in the endocytic pathway: immunological functions of gamma-interferon-inducible lysosomal thiol reductase. Antioxid Redox Signal 15(3):657–668.  https://doi.org/10.1089/ars.2010.3684CrossRefPubMedPubMedCentralGoogle Scholar
  79. Herrero R, Quint W, Hildesheim A, Gonzalez P, Struijk L, Katki HA et al (2013) Reduced prevalence of oral human papillomavirus (HPV) 4 years after bivalent HPV vaccination in a randomized clinical trial in Costa Rica. PLoS One 8(7):e68329.  https://doi.org/10.1371/journal.pone.0068329CrossRefPubMedPubMedCentralGoogle Scholar
  80. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723.  https://doi.org/10.1056/NEJMoa1003466CrossRefPubMedPubMedCentralGoogle Scholar
  81. Hu W, Li X, Zhang C, Yang Y, Jiang J, Wu C (2016) Tumor-associated macrophages in cancers. Clin Transl Oncol 18(3):251–258.  https://doi.org/10.1007/s12094-015-1373-0CrossRefPubMedPubMedCentralGoogle Scholar
  82. Huang J, El-Gamil M, Dudley ME, Li YF, Rosenberg SA, Robbins PF (2004) T cells associated with tumor regression recognize frameshifted products of the CDKN2A tumor suppressor gene locus and a mutated HLA class I gene product. J Immunol 172(10):6057–6064PubMedPubMedCentralCrossRefGoogle Scholar
  83. Huh WK, Joura EA, Giuliano AR, Iversen OE, de Andrade RP, Ault KA et al (2017) Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial. Lancet 390(10108):2143–2159.  https://doi.org/10.1016/S0140-6736(17)31821-4CrossRefPubMedPubMedCentralGoogle Scholar
  84. Inoue S, Leitner WW, Golding B, Scott D (2006) Inhibitory effects of B cells on antitumor immunity. Cancer Res 66(15):7741–7747PubMedCrossRefPubMedCentralGoogle Scholar
  85. Inozume T, Hanada K, Wang QJ, Ahmadzadeh M, Wunderlich JR, Rosenberg SA et al (2010) Selection of CD8+PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells. J Immunother 33(9):956–964.  https://doi.org/10.1097/CJI.0b013e3181fad2b0CrossRefPubMedPubMedCentralGoogle Scholar
  86. Iwakura Y, Ishigame H, Saijo S, Nakae S (2011) Functional specialization of interleukin-17 family members. Immunity 34(2):149–162.  https://doi.org/10.1016/j.immuni.2011.02.012CrossRefPubMedPubMedCentralGoogle Scholar
  87. Jomaa H, Feurle J, Luhs K, Kunzmann V, Tony HP, Herderich M et al (1999) Vgamma9/Vdelta2 T cell activation induced by bacterial low molecular mass compounds depends on the 1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid biosynthesis. FEMS Immunol Med Microbiol 25(4):371–378PubMedPubMedCentralGoogle Scholar
  88. Josefowicz SZ, Lu LF, Rudensky AY (2012) Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 30:531–564.  https://doi.org/10.1146/annurev.immunol.25.022106.141623CrossRefPubMedPubMedCentralGoogle Scholar
  89. Jung KY, Cho SW, Kim YA, Kim D, Oh BC, Park DJ et al (2015) Cancers with higher density of tumor-associated macrophages were associated with poor survival rates. J Pathol Transl Med 49(4):318–324.  https://doi.org/10.4132/jptm.2015.06.01CrossRefPubMedPubMedCentralGoogle Scholar
  90. Kabelitz D, Wesch D, Pitters E, Zoller M (2004) Characterization of tumor reactivity of human V gamma 9V delta 2 gamma delta T cells in vitro and in SCID mice in vivo. J Immunol 173(11):6767–6776PubMedCrossRefPubMedCentralGoogle Scholar
  91. Kabelitz D, Wesch D, He W (2007) Perspectives of gammadelta T cells in tumor immunology. Cancer Res 67(1):5–8PubMedCrossRefPubMedCentralGoogle Scholar
  92. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF et al (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363(5):411–422.  https://doi.org/10.1056/NEJMoa1001294CrossRefPubMedPubMedCentralGoogle Scholar
  93. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ et al (1998) Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci U S A 95(13):7556–7561PubMedPubMedCentralCrossRefGoogle Scholar
  94. Kato Y, Tanaka Y, Miyagawa F, Yamashita S, Minato N (2001) Targeting of tumor cells for human gammadelta T cells by nonpeptide antigens. J Immunol 167(9):5092–5098PubMedCrossRefPubMedCentralGoogle Scholar
  95. Kawakami Y, Wang X, Shofuda T, Sumimoto H, Tupesis J, Fitzgerald E et al (2001) Isolation of a new melanoma antigen, MART-2, containing a mutated epitope recognized by autologous tumor-infiltrating T lymphocytes. J Immunol 166(4):2871–2877PubMedCrossRefPubMedCentralGoogle Scholar
  96. Kerkar SP, Restifo NP (2012) Cellular constituents of immune escape within the tumor microenvironment. Cancer Res 72(13):3125–3130.  https://doi.org/10.1158/0008-5472.CAN-11-4094CrossRefPubMedPubMedCentralGoogle Scholar
  97. Klapper JA, Downey SG, Smith FO, Yang JC, Hughes MS, Kammula US et al (2008) High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma: a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer 113(2):293–301.  https://doi.org/10.1002/cncr.23552CrossRefPubMedPubMedCentralGoogle Scholar
  98. Knutson KL, Disis ML (2005) Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother 54(8):721–728PubMedCrossRefPubMedCentralGoogle Scholar
  99. Kobayashi H, Tanaka Y, Yagi J, Toma H, Uchiyama T (2001) Gamma/delta T cells provide innate immunity against renal cell carcinoma. Cancer Immunol Immunother 50(3):115–124PubMedCrossRefPubMedCentralGoogle Scholar
  100. Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 Cells. Annu Rev Immunol 27:485–517.  https://doi.org/10.1146/annurev.immunol.021908.132710CrossRefPubMedPubMedCentralGoogle Scholar
  101. Krummel MF, Allison JP (1996) CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J Exp Med 183(6):2533–2540PubMedCrossRefPubMedCentralGoogle Scholar
  102. Kryczek I, Wei S, Szeliga W, Vatan L, Zou W (2009a) Endogenous IL-17 contributes to reduced tumor growth and metastasis. Blood 114(2):357–359.  https://doi.org/10.1182/blood-2008-09-177360CrossRefPubMedPubMedCentralGoogle Scholar
  103. Kryczek I, Banerjee M, Cheng P, Vatan L, Szeliga W, Wei S et al (2009b) Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114(6):1141–1149.  https://doi.org/10.1182/blood-2009-03-208249CrossRefPubMedPubMedCentralGoogle Scholar
  104. Kunzmann V, Bauer E, Feurle J, Weissinger F, Tony HP, Wilhelm M (2000) Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood 96(2):384–392PubMedPubMedCentralGoogle Scholar
  105. Laborde RR, Lin Y, Gustafson MP, Bulur PA, Dietz AB (2014) Cancer vaccines in the world of immune suppressive monocytes (CD14(+)HLA-DR(lo/neg) cells): the gateway to improved responses. Front Immunol 5:147.  https://doi.org/10.3389/fimmu.2014.00147CrossRefPubMedPubMedCentralGoogle Scholar
  106. Lakshminarayanan V, Thompson P, Wolfert MA, Buskas T, Bradley JM, Pathangey LB et al (2012) Immune recognition of tumor-associated mucin MUC1 is achieved by a fully synthetic aberrantly glycosylated MUC1 tripartite vaccine. Proc Natl Acad Sci U S A 109(1):261–266.  https://doi.org/10.1073/pnas.1115166109CrossRefPubMedPubMedCentralGoogle Scholar
  107. Landsberg J, Kohlmeyer J, Renn M, Bald T, Rogava M, Cron M et al (2012) Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation. Nature 490(7420):412–416.  https://doi.org/10.1038/nature11538CrossRefPubMedPubMedCentralGoogle Scholar
  108. Lang F, Peyrat MA, Constant P, Davodeau F, David-Ameline J, Poquet Y et al (1995) Early activation of human V gamma 9V delta 2 T cell broad cytotoxicity and TNF production by nonpeptidic mycobacterial ligands. J Immunol 154(11):5986–5994PubMedPubMedCentralGoogle Scholar
  109. Lasek W, Zagozdzon R, Jakobisiak M (2014) Interleukin 12: still a promising candidate for tumor immunotherapy? Cancer Immunol Immunother 63(5):419–435.  https://doi.org/10.1007/s00262-014-1523-1CrossRefPubMedPubMedCentralGoogle Scholar
  110. Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I et al (2001) PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2(3):261–268.  https://doi.org/10.1038/85330CrossRefPubMedPubMedCentralGoogle Scholar
  111. Lee JC, Lee KM, Kim DW, Heo DS (2004) Elevated TGF-beta1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients. J Immunol 172(12):7335–7340PubMedCrossRefPubMedCentralGoogle Scholar
  112. Lehtinen M, Paavonen J, Wheeler CM, Jaisamrarn U, Garland SM, Castellsague X et al (2012) Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol 13(1):89–99.  https://doi.org/10.1016/S1470-2045(11)70286-8CrossRefPubMedPubMedCentralGoogle Scholar
  113. Lennerz V, Fatho M, Gentilini C, Frye RA, Lifke A, Ferel D et al (2005) The response of autologous T cells to a human melanoma is dominated by mutated neoantigens. Proc Natl Acad Sci U S A 102(44):16013–16018PubMedPubMedCentralCrossRefGoogle Scholar
  114. Li MO, Flavell RA (2008) TGF-beta: a master of all T cell trades. Cell 134(3):392–404.  https://doi.org/10.1016/j.cell.2008.07.025CrossRefPubMedPubMedCentralGoogle Scholar
  115. Li Y, Wang Q, Mariuzza RA (2011) Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6. J Exp Med 208(4):703–714.  https://doi.org/10.1084/jem.20102548CrossRefPubMedPubMedCentralGoogle Scholar
  116. Li Q, Han Y, Fei G, Guo Z, Ren T, Liu Z (2012) IL-17 promoted metastasis of non-small-cell lung cancer cells. Immunol Lett 148(2):144–150.  https://doi.org/10.1016/j.imlet.2012.10.011CrossRefPubMedPubMedCentralGoogle Scholar
  117. Linard B, Bezieau S, Benlalam H, Labarriere N, Guilloux Y, Diez E et al (2002) A ras-mutated peptide targeted by CTL infiltrating a human melanoma lesion. J Immunol 168(9):4802–4808PubMedCrossRefPubMedCentralGoogle Scholar
  118. Lindsten T, Lee KP, Harris ES, Petryniak B, Craighead N, Reynolds PJ et al (1993) Characterization of CTLA-4 structure and expression on human T cells. J Immunol 151(7):3489–3499PubMedPubMedCentralGoogle Scholar
  119. Linsley PS, Greene JL, Brady W, Bajorath J, Ledbetter JA, Peach R (1994) Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1(9):793–801PubMedCrossRefPubMedCentralGoogle Scholar
  120. Liu Z, Guo BL, Gehrs BC, Nan L, Lopez RD (2005) Ex vivo expanded human Vgamma9Vdelta2+ gammadelta-T cells mediate innate antitumor activity against human prostate cancer cells in vitro. J Urol 173(5):1552–1556PubMedCrossRefPubMedCentralGoogle Scholar
  121. Loewenstein MS, Zamcheck N (1978) Carcinoembryonic antigen (CEA) levels in benign gastrointestinal disease states. Cancer 42(3 Suppl):1412–1418PubMedCrossRefPubMedCentralGoogle Scholar
  122. Lozupone F, Pende D, Burgio VL, Castelli C, Spada M, Venditti M et al (2004) Effect of human natural killer and gammadelta T cells on the growth of human autologous melanoma xenografts in SCID mice. Cancer Res 64(1):378–385PubMedCrossRefPubMedCentralGoogle Scholar
  123. Lyakh L, Trinchieri G, Provezza L, Carra G, Gerosa F (2008) Regulation of interleukin-12/interleukin-23 production and the T-helper 17 response in humans. Immunol Rev 226:112–131.  https://doi.org/10.1111/j.1600-065X.2008.00700.xCrossRefPubMedPubMedCentralGoogle Scholar
  124. Makita M, Azuma T, Hamaguchi H, Niiya H, Kojima K, Fujita S et al (2002) Leukemia-associated fusion proteins, dek-can and bcr-abl, represent immunogenic HLA-DR-restricted epitopes recognized by fusion peptide-specific CD4+ T lymphocytes. Leukemia 16(12):2400–2407PubMedCrossRefPubMedCentralGoogle Scholar
  125. Malkovska V, Cigel FK, Armstrong N, Storer BE, Hong R (1992) Antilymphoma activity of human gamma delta T-cells in mice with severe combined immune deficiency. Cancer Res 52(20):5610–5616PubMedPubMedCentralGoogle Scholar
  126. Mantovani A, Allavena P (2015) The interaction of anticancer therapies with tumor-associated macrophages. J Exp Med 212(4):435–445.  https://doi.org/10.1084/jem.20150295CrossRefPubMedPubMedCentralGoogle Scholar
  127. Mariani S, Muraro M, Pantaleoni F, Fiore F, Nuschak B, Peola S et al (2005) Effector gammadelta T cells and tumor cells as immune targets of zoledronic acid in multiple myeloma. Leukemia 19(4):664–670PubMedCrossRefPubMedCentralGoogle Scholar
  128. Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S et al (2009) T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 31(5):787–798.  https://doi.org/10.1016/j.immuni.2009.09.014CrossRefPubMedPubMedCentralGoogle Scholar
  129. Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L et al (2006) A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part II: immunization of adults. MMWR Recomm Rep 55(RR-16):1–33. quiz CE1–4PubMedPubMedCentralGoogle Scholar
  130. Mathai AM, Kapadia MJ, Alexander J, Kernochan LE, Swanson PE, Yeh MM (2012) Role of Foxp3-positive tumor-infiltrating lymphocytes in the histologic features and clinical outcomes of hepatocellular carcinoma. Am J Surg Pathol 36(7):980–986.  https://doi.org/10.1097/PAS.0b013e31824e9b7cCrossRefPubMedPubMedCentralGoogle Scholar
  131. McClanahan J, Fukushima PI, Stetler-Stevenson M (1999) Increased peripheral blood gamma delta T-cells in patients with lymphoid neoplasia: a diagnostic dilemma in flow cytometry. Cytometry 38(6):280–285PubMedCrossRefPubMedCentralGoogle Scholar
  132. McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK et al (2016) Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351(6280):1463–1469.  https://doi.org/10.1126/science.aaf1490CrossRefPubMedPubMedCentralGoogle Scholar
  133. Meng XY, Zhou CH, Ma J, Jiang C, Ji P (2012) Expression of interleukin-17 and its clinical significance in gastric cancer patients. Med Oncol 29(5):3024–3028.  https://doi.org/10.1007/s12032-012-0273-1CrossRefPubMedPubMedCentralGoogle Scholar
  134. Meyer C, Cagnon L, Costa-Nunes CM, Baumgaertner P, Montandon N, Leyvraz L et al (2014) Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol Immunother 63(3):247–257.  https://doi.org/10.1007/s00262-013-1508-5CrossRefPubMedPubMedCentralGoogle Scholar
  135. Miracco C, Mourmouras V, Biagioli M, Rubegni P, Mannucci S, Monciatti I et al (2007) Utility of tumour-infiltrating CD25+FOXP3+ regulatory T cell evaluation in predicting local recurrence in vertical growth phase cutaneous melanoma. Oncol Rep 18(5):1115–1122PubMedPubMedCentralGoogle Scholar
  136. Mocellin S, Nitti D (2008) TNF and cancer: the two sides of the coin. Front Biosci 13:2774–2783PubMedCrossRefPubMedCentralGoogle Scholar
  137. Mookerjee-Basu J, Vantourout P, Martinez LO, Perret B, Collet X, Perigaud C et al (2010) F1-adenosine triphosphatase displays properties characteristic of an antigen presentation molecule for Vgamma9Vdelta2 T cells. J Immunol 184(12):6920–6928.  https://doi.org/10.4049/jimmunol.0904024CrossRefPubMedPubMedCentralGoogle Scholar
  138. Morita CT, Beckman EM, Bukowski JF, Tanaka Y, Band H, Bloom BR et al (1995) Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gamma delta T cells. Immunity 3(4):495–507PubMedCrossRefPubMedCentralGoogle Scholar
  139. Morita CT, Jin C, Sarikonda G, Wang H (2007) Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens. Immunol Rev 215:59–76PubMedCrossRefPubMedCentralGoogle Scholar
  140. Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H et al (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58(16):3491–3494PubMedPubMedCentralGoogle Scholar
  141. Neefjes J, Jongsma ML, Paul P, Bakke O (2011) Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol 11(12):823–836.  https://doi.org/10.1038/nri3084CrossRefPubMedPubMedCentralGoogle Scholar
  142. Nicholaou T, Ebert L, Davis ID, Robson N, Klein O, Maraskovsky E et al (2006) Directions in the immune targeting of cancer: lessons learned from the cancer-testis Ag NY-ESO-1. Immunol Cell Biol 84(3):303–317PubMedCrossRefPubMedCentralGoogle Scholar
  143. Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE (2014) Abeloff’s clinical oncology, 5th edn. Elsevier Saunders, PhiladelphiaGoogle Scholar
  144. Nishimura H, Nose M, Hiai H, Minato N, Honjo T (1999) Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11(2):141–151PubMedCrossRefPubMedCentralGoogle Scholar
  145. Noguchi T, Ward JP, Gubin MM, Arthur CD, Lee SH, Hundal J et al (2017) Temporally distinct PD-L1 expression by tumor and host cells contributes to immune escape. Cancer Immunol Res 5(2):106–117.  https://doi.org/10.1158/2326-6066.CIR-16-0391CrossRefPubMedPubMedCentralGoogle Scholar
  146. Novellino L, Renkvist N, Rini F, Mazzocchi A, Rivoltini L, Greco A et al (2003) Identification of a mutated receptor-like protein tyrosine phosphatase kappa as a novel, class II HLA-restricted melanoma antigen. J Immunol 170(12):6363–6370PubMedCrossRefPubMedCentralGoogle Scholar
  147. Ohno S, Inagawa H, Dhar DK, Fujii T, Ueda S, Tachibana M et al (2003) The degree of macrophage infiltration into the cancer cell nest is a significant predictor of survival in gastric cancer patients. Anticancer Res 23(6D):5015–5022PubMedPubMedCentralGoogle Scholar
  148. Ohri CM, Shikotra A, Green RH, Waller DA, Bradding P (2009) Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1 phenotype associated with extended survival. Eur Respir J 33(1):118–126.  https://doi.org/10.1183/09031936.00065708CrossRefPubMedPubMedCentralGoogle Scholar
  149. Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ et al (2017) An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547(7662):217–221.  https://doi.org/10.1038/nature22991CrossRefPubMedPubMedCentralGoogle Scholar
  150. Otto M, Barfield RC, Martin WJ, Iyengar R, Leung W, Leimig T et al (2005) Combination immunotherapy with clinical-scale enriched human gammadelta T cells, hu14.18 antibody, and the immunocytokine Fc-IL7 in disseminated neuroblastoma. Clin Cancer Res 11(23):8486–8491PubMedCrossRefPubMedCentralGoogle Scholar
  151. Paavonen J, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter D et al (2009) Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet 374(9686):301–314.  https://doi.org/10.1016/S0140-6736(09)61248-4CrossRefPubMedPubMedCentralGoogle Scholar
  152. Palefsky JM, Giuliano AR, Goldstone S, Moreira ED Jr, Aranda C, Jessen H et al (2011) HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 365(17):1576–1585.  https://doi.org/10.1056/NEJMoa1010971CrossRefPubMedPubMedCentralGoogle Scholar
  153. Palucka K, Banchereau J (2012) Cancer immunotherapy via dendritic cells. Nat Rev Cancer 12(4):265–277.  https://doi.org/10.1038/nrc3258CrossRefPubMedPubMedCentralGoogle Scholar
  154. Peggs KS, Quezada SA, Chambers CA, Korman AJ, Allison JP (2009) Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med 206(8):1717–1725.  https://doi.org/10.1084/jem.20082492CrossRefPubMedPubMedCentralGoogle Scholar
  155. Peng G, Wang HY, Peng W, Kiniwa Y, Seo KH, Wang RF (2007) Tumor-infiltrating gammadelta T cells suppress T and dendritic cell function via mechanisms controlled by a unique toll-like receptor signaling pathway. Immunity 27(2):334–348PubMedCrossRefPubMedCentralGoogle Scholar
  156. Penn I (1996) Malignant melanoma in organ allograft recipients. Transplantation 61(2):274–278PubMedCrossRefPubMedCentralGoogle Scholar
  157. Pereira-Faca SR, Kuick R, Puravs E, Zhang Q, Krasnoselsky AL, Phanstiel D et al (2007) Identification of 14-3-3 theta as an antigen that induces a humoral response in lung cancer. Cancer Res 67(24):12000–12006.  https://doi.org/10.1158/0008-5472.CAN-07-2913CrossRefPubMedPubMedCentralGoogle Scholar
  158. Peters A, Lee Y, Kuchroo VK (2011) The many faces of Th17 cells. Curr Opin Immunol 23(6):702–706.  https://doi.org/10.1016/j.coi.2011.08.007CrossRefPubMedPubMedCentralGoogle Scholar
  159. Petrella T, Quirt I, Verma S, Haynes AE, Charette M, Bak K (2007) Single-agent interleukin-2 in the treatment of metastatic melanoma: a systematic review. Cancer Treat Rev 33(5):484–496PubMedCrossRefPubMedCentralGoogle Scholar
  160. Pham SM, Kormos RL, Landreneau RJ, Kawai A, Gonzalez-Cancel I, Hardesty RL et al (1995) Solid tumors after heart transplantation: lethality of lung cancer. Ann Thorac Surg 60(6):1623–1626PubMedCrossRefPubMedCentralGoogle Scholar
  161. Poggi A, Venturino C, Catellani S, Clavio M, Miglino M, Gobbi M et al (2004) Vdelta1 T lymphocytes from B-CLL patients recognize ULBP3 expressed on leukemic B cells and up-regulated by trans-retinoic acid. Cancer Res 64(24):9172–9179PubMedCrossRefPubMedCentralGoogle Scholar
  162. Qureshi OS, Zheng Y, Nakamura K, Attridge K, Manzotti C, Schmidt EM et al (2011) Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 332(6029):600–603.  https://doi.org/10.1126/science.1202947CrossRefPubMedPubMedCentralGoogle Scholar
  163. Rajasagi M, Shukla SA, Fritsch EF, Keskin DB, DeLuca D, Carmona E et al (2014) Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia. Blood 124(3):453–462.  https://doi.org/10.1182/blood-2014-04-567933CrossRefPubMedPubMedCentralGoogle Scholar
  164. Rausch MP, Irvine KR, Antony PA, Restifo NP, Cresswell P, Hastings KT (2010) GILT accelerates autoimmunity to the melanoma antigen tyrosinase-related protein 1. J Immunol 185(5):2828–2835.  https://doi.org/10.4049/jimmunol.1000945CrossRefPubMedPubMedCentralGoogle Scholar
  165. Redjimi N, Raffin C, Raimbaud I, Pignon P, Matsuzaki J, Odunsi K et al (2012) CXCR3+ T regulatory cells selectively accumulate in human ovarian carcinomas to limit type I immunity. Cancer Res 72(17):4351–4360.  https://doi.org/10.1158/0008-5472.CAN-12-0579CrossRefPubMedPubMedCentralGoogle Scholar
  166. Ribas A, Shin DS, Zaretsky J, Frederiksen J, Cornish A, Avramis E et al (2016) PD-1 blockade expands intratumoral memory T cells. Cancer Immunol Res 4(3):194–203.  https://doi.org/10.1158/2326-6066.CIR-15-0210CrossRefPubMedPubMedCentralGoogle Scholar
  167. Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V et al (2014) Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell 25(6):846–859.  https://doi.org/10.1016/j.ccr.2014.05.016CrossRefPubMedPubMedCentralGoogle Scholar
  168. Rizza P, Capone I, Moretti F, Proietti E, Belardelli F (2011) IFN-alpha as a vaccine adjuvant: recent insights into the mechanisms and perspectives for its clinical use. Expert Rev Vaccines 10(4):487–498.  https://doi.org/10.1586/erv.11.9CrossRefPubMedPubMedCentralGoogle Scholar
  169. Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C et al (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364(26):2517–2526.  https://doi.org/10.1056/NEJMoa1104621CrossRefPubMedPubMedCentralGoogle Scholar
  170. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L et al (2015) Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372(26):2521–2532.  https://doi.org/10.1056/NEJMoa1503093CrossRefPubMedPubMedCentralGoogle Scholar
  171. van Rooij N, van Buuren MM, Philips D, Velds A, Toebes M, Heemskerk B et al (2013) Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J Clin Oncol Off J Am Soc Clin Oncol 31(32):e439–e442.  https://doi.org/10.1200/JCO.2012.47.7521CrossRefGoogle Scholar
  172. Rosenberg SA (2012) Raising the bar: the curative potential of human cancer immunotherapy. Sci Transl Med 4(127):127ps8.  https://doi.org/10.1126/scitranslmed.3003634CrossRefPubMedPubMedCentralGoogle Scholar
  173. Ruas M, Peters G (1998) The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochim Biophys Acta 1378(2):F115–F177PubMedPubMedCentralGoogle Scholar
  174. Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P (1997) Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 275(5307):1790–1792PubMedCrossRefPubMedCentralGoogle Scholar
  175. Ruffell B, Chang-Strachan D, Chan V, Rosenbusch A, Ho CM, Pryer N et al (2014) Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell 26(5):623–637.  https://doi.org/10.1016/j.ccell.2014.09.006CrossRefPubMedPubMedCentralGoogle Scholar
  176. Sadelain M (2017) CD19 CAR T cells. Cell 171(7):1471.  https://doi.org/10.1016/j.cell.2017.12.002CrossRefPubMedPubMedCentralGoogle Scholar
  177. Sahin U, Derhovanessian E, Miller M, Kloke BP, Simon P, Lower M et al (2017) Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547(7662):222–226.  https://doi.org/10.1038/nature23003CrossRefPubMedPubMedCentralGoogle Scholar
  178. Sato K, Kimura S, Segawa H, Yokota A, Matsumoto S, Kuroda J et al (2005a) Cytotoxic effects of gammadelta T cells expanded ex vivo by a third generation bisphosphonate for cancer immunotherapy. Int J Cancer 116(1):94–99PubMedCrossRefPubMedCentralGoogle Scholar
  179. Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F et al (2005b) Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A 102(51):18538–18543PubMedPubMedCentralCrossRefGoogle Scholar
  180. Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT (2002) Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev 188:22–32PubMedCrossRefPubMedCentralGoogle Scholar
  181. Scardino A, Gross DA, Alves P, Schultze JL, Graff-Dubois S, Faure O et al (2002) HER-2/neu and hTERT cryptic epitopes as novel targets for broad spectrum tumor immunotherapy. J Immunol 168(11):5900–5906PubMedCrossRefPubMedCentralGoogle Scholar
  182. Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331(6024):1565–1570.  https://doi.org/10.1126/science.1203486CrossRefPubMedPubMedCentralGoogle Scholar
  183. Schroder K, Hertzog PJ, Ravasi T, Hume DA (2004) Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 75(2):163–189.  https://doi.org/10.1189/jlb.0603252CrossRefPubMedPubMedCentralGoogle Scholar
  184. Schubbert S, Shannon K, Bollag G (2007) Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer 7(4):295–308PubMedCrossRefPubMedCentralGoogle Scholar
  185. Selin LK, Stewart S, Shen C, Mao HQ, Wilkins JA (1992) Reactivity of gamma delta T cells induced by the tumour cell line RPMI 8226: functional heterogeneity of clonal populations and role of GroEL heat shock proteins. Scand J Immunol 36(1):107–117PubMedCrossRefPubMedCentralGoogle Scholar
  186. Sensi M, Nicolini G, Zanon M, Colombo C, Molla A, Bersani I et al (2005) Immunogenicity without immunoselection: a mutant but functional antioxidant enzyme retained in a human metastatic melanoma and targeted by CD8(+) T cells with a memory phenotype. Cancer Res 65(2):632–640PubMedPubMedCentralGoogle Scholar
  187. Shah S, Divekar AA, Hilchey SP, Cho HM, Newman CL, Shin SU et al (2005) Increased rejection of primary tumors in mice lacking B cells: inhibition of anti-tumor CTL and TH1 cytokine responses by B cells. Int J Cancer 117(4):574–586PubMedCrossRefPubMedCentralGoogle Scholar
  188. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ et al (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410(6832):1107–1111PubMedCrossRefPubMedCentralGoogle Scholar
  189. Sharkey MS, Lizee G, Gonzales MI, Patel S, Topalian SL (2004) CD4(+) T-cell recognition of mutated B-RAF in melanoma patients harboring the V599E mutation. Cancer Res 64(5):1595–1599PubMedCrossRefPubMedCentralGoogle Scholar
  190. Sheil AG (1986) Cancer after transplantation. World J Surg 10(3):389–396PubMedCrossRefPubMedCentralGoogle Scholar
  191. Sheppard KA, Fitz LJ, Lee JM, Benander C, George JA, Wooters J et al (2004) PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to PKCtheta. FEBS Lett 574(1–3):37–41.  https://doi.org/10.1016/j.febslet.2004.07.083CrossRefPubMedPubMedCentralGoogle Scholar
  192. Sicard H, Al Saati T, Delsol G, Fournie JJ (2001) Synthetic phosphoantigens enhance human Vgamma9Vdelta2 T lymphocytes killing of non-Hodgkin's B lymphoma. Mol Med 7(10):711–722PubMedPubMedCentralCrossRefGoogle Scholar
  193. Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K, Arce F et al (2013) Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med 210(9):1695–1710.  https://doi.org/10.1084/jem.20130579CrossRefPubMedPubMedCentralGoogle Scholar
  194. Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M et al (2000) Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med 191(4):661–668PubMedPubMedCentralCrossRefGoogle Scholar
  195. Smyth MJ, Crowe NY, Godfrey DI (2001) NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int Immunol 13(4):459–463PubMedCrossRefPubMedCentralGoogle Scholar
  196. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A et al (2014) Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 371(23):2189–2199.  https://doi.org/10.1056/NEJMoa1406498CrossRefPubMedPubMedCentralGoogle Scholar
  197. Solito S, Falisi E, Diaz-Montero CM, Doni A, Pinton L, Rosato A et al (2011) A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells. Blood 118(8):2254–2265.  https://doi.org/10.1182/blood-2010-12-325753CrossRefPubMedPubMedCentralGoogle Scholar
  198. Somasundaram R, Swoboda R, Caputo L, Otvos L, Weber B, Volpe P et al (2006) Human leukocyte antigen-A2-restricted CTL responses to mutated BRAF peptides in melanoma patients. Cancer Res 66(6):3287–3293.  https://doi.org/10.1158/0008-5472.CAN-05-1932CrossRefPubMedPubMedCentralGoogle Scholar
  199. Steel JC, Waldmann TA, Morris JC (2012) Interleukin-15 biology and its therapeutic implications in cancer. Trends Pharmacol Sci 33(1):35–41.  https://doi.org/10.1016/j.tips.2011.09.004CrossRefPubMedPubMedCentralGoogle Scholar
  200. Street SE, Cretney E, Smyth MJ (2001) Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97(1):192–197PubMedCrossRefPubMedCentralGoogle Scholar
  201. Street SE, Trapani JA, MacGregor D, Smyth MJ (2002) Suppression of lymphoma and epithelial malignancies effected by interferon gamma. J Exp Med 196(1):129–134PubMedPubMedCentralCrossRefGoogle Scholar
  202. Talmadge JE, Gabrilovich DI (2013) History of myeloid-derived suppressor cells. Nat Rev Cancer 13(10):739–752.  https://doi.org/10.1038/nrc3581CrossRefPubMedPubMedCentralGoogle Scholar
  203. Tannenbaum CS, Hamilton TA (2000) Immune-inflammatory mechanisms in IFNgamma-mediated anti-tumor activity. Semin Cancer Biol 10(2):113–123PubMedCrossRefPubMedCentralGoogle Scholar
  204. Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL et al (2012) Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 4(127):127ra37.  https://doi.org/10.1126/scitranslmed.3003689CrossRefPubMedPubMedCentralGoogle Scholar
  205. Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH et al (2014) Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res 20(19):5064–5074.  https://doi.org/10.1158/1078-0432.CCR-13-3271CrossRefPubMedPubMedCentralGoogle Scholar
  206. Teng MW, Swann JB, Koebel CM, Schreiber RD, Smyth MJ (2008) Immune-mediated dormancy: an equilibrium with cancer. J Leukoc Biol 84(4):988–993.  https://doi.org/10.1189/jlb.1107774CrossRefPubMedPubMedCentralGoogle Scholar
  207. Tham M, Khoo K, Yeo KP, Kato M, Prevost-Blondel A, Angeli V et al (2015) Macrophage depletion reduces postsurgical tumor recurrence and metastatic growth in a spontaneous murine model of melanoma. Oncotarget 6(26):22857–22868.  https://doi.org/10.18632/oncotarget.3127CrossRefPubMedPubMedCentralGoogle Scholar
  208. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH (1995) Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3(5):541–547PubMedCrossRefPubMedCentralGoogle Scholar
  209. Topalian SL, Gonzales MI, Ward Y, Wang X, Wang RF (2002) Revelation of a cryptic major histocompatibility complex class II-restricted tumor epitope in a novel RNA-processing enzyme. Cancer Res 62(19):5505–5509PubMedPubMedCentralGoogle Scholar
  210. Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L et al (2016) T-cell transfer therapy targeting mutant KRAS in cancer. N Engl J Med 375(23):2255–2262.  https://doi.org/10.1056/NEJMoa1609279CrossRefPubMedPubMedCentralGoogle Scholar
  211. Trefzer U, Hofmann M, Reinke S, Guo YJ, Audring H, Spagnoli G et al (2006) Concordant loss of melanoma differentiation antigens in synchronous and asynchronous melanoma metastases: implications for immunotherapy. Melanoma Res 16(2):137–145PubMedCrossRefPubMedCentralGoogle Scholar
  212. Trinchieri G (2010) Type I interferon: friend or foe? J Exp Med 207(10):2053–2063.  https://doi.org/10.1084/jem.20101664CrossRefPubMedPubMedCentralGoogle Scholar
  213. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L et al (2014) PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515(7528):568–571.  https://doi.org/10.1038/nature13954CrossRefPubMedPubMedCentralGoogle Scholar
  214. Tuthill RJ, Unger JM, Liu PY, Flaherty LE, Sondak VK (2002) Risk assessment in localized primary cutaneous melanoma: a Southwest Oncology Group study evaluating nine factors and a test of the Clark logistic regression prediction model. Am J Clin Pathol 118(4):504–511.  https://doi.org/10.1309/WBF7-N8KH-71KT-RVQ9CrossRefPubMedPubMedCentralGoogle Scholar
  215. Ueno H, Klechevsky E, Morita R, Aspord C, Cao T, Matsui T et al (2007) Dendritic cell subsets in health and disease. Immunol Rev 219:118–142PubMedCrossRefPubMedCentralGoogle Scholar
  216. Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L et al (2015) Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350(6257):207–211.  https://doi.org/10.1126/science.aad0095CrossRefPubMedPubMedCentralGoogle Scholar
  217. Vaughn CP, Zobell SD, Furtado LV, Baker CL, Samowitz WS (2011) Frequency of KRAS, BRAF, and NRAS mutations in colorectal cancer. Genes Chromosomes Cancer 50(5):307–312.  https://doi.org/10.1002/gcc.20854CrossRefPubMedPubMedCentralGoogle Scholar
  218. Venna SS, Thummala S, Nosrati M, Leong SP, Miller JR 3rd, Sagebiel RW et al (2012) Analysis of sentinel lymph node positivity in patients with thin primary melanoma. J Am Acad Dermatol 68:560–567.  https://doi.org/10.1016/j.jaad.2012.08.045CrossRefPubMedPubMedCentralGoogle Scholar
  219. Viey E, Fromont G, Escudier B, Morel Y, Da Rocha S, Chouaib S et al (2005) Phosphostim-activated gamma delta T cells kill autologous metastatic renal cell carcinoma. J Immunol 174(3):1338–1347PubMedCrossRefPubMedCentralGoogle Scholar
  220. Viguier M, Lemaitre F, Verola O, Cho MS, Gorochov G, Dubertret L et al (2004) Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J Immunol 173(2):1444–1453PubMedCrossRefPubMedCentralGoogle Scholar
  221. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL et al (2011) Innate or adaptive immunity? The example of natural killer cells. Science 331(6013):44–49.  https://doi.org/10.1126/science.1198687CrossRefPubMedPubMedCentralGoogle Scholar
  222. 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(4):239–252.  https://doi.org/10.1038/nri3174CrossRefPubMedPubMedCentralGoogle Scholar
  223. von Lilienfeld-Toal M, Nattermann J, Feldmann G, Sievers E, Frank S, Strehl J et al (2006) Activated gammadelta T cells express the natural cytotoxicity receptor natural killer p 44 and show cytotoxic activity against myeloma cells. Clin Exp Immunol 144(3):528–533CrossRefGoogle Scholar
  224. Waldmann TA (2006) The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol 6(8):595–601PubMedCrossRefPubMedCentralGoogle Scholar
  225. Walunas TL, Lenschow DJ, Bakker CY, Linsley PS, Freeman GJ, Green JM et al (1994) CTLA-4 can function as a negative regulator of T cell activation. Immunity 1(5):405–413PubMedCrossRefPubMedCentralGoogle Scholar
  226. Wang Z, Margulies L, Hicklin DJ, Ferrone S (1996) Molecular and functional phenotypes of melanoma cells with abnormalities in HLA class I antigen expression. Tissue Antigens 47(5):382–390PubMedCrossRefPubMedCentralGoogle Scholar
  227. Wang HY, Zhou J, Zhu K, Riker AI, Marincola FM, Wang RF (2002) Identification of a mutated fibronectin as a tumor antigen recognized by CD4+ T cells: its role in extracellular matrix formation and tumor metastasis. J Exp Med 195(11):1397–1406PubMedPubMedCentralCrossRefGoogle Scholar
  228. Wang HY, Lee DA, Peng G, Guo Z, Li Y, Kiniwa Y et al (2004) Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity 20(1):107–118PubMedCrossRefPubMedCentralGoogle Scholar
  229. Wang HY, Peng G, Guo Z, Shevach EM, Wang RF (2005) Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells. J Immunol 174(5):2661–2670PubMedCrossRefPubMedCentralGoogle Scholar
  230. Wang ZK, Yang B, Liu H, Hu Y, Yang JL, Wu LL et al (2012) Regulatory T cells increase in breast cancer and in stage IV breast cancer. Cancer Immunol Immunother 61(6):911–916.  https://doi.org/10.1007/s00262-011-1158-4CrossRefPubMedPubMedCentralGoogle Scholar
  231. Weber J, Gibney G, Kudchadkar R, Yu B, Cheng P, Martinez AJ et al (2016) Phase I/II study of metastatic melanoma patients treated with nivolumab who had progressed after ipilimumab. Cancer Immunol Res 4(4):345–353.  https://doi.org/10.1158/2326-6066.CIR-15-0193CrossRefPubMedPubMedCentralGoogle Scholar
  232. Wheeler CM, Castellsague X, Garland SM, Szarewski A, Paavonen J, Naud P et al (2012) Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol 13(1):100–110.  https://doi.org/10.1016/S1470-2045(11)70287-XCrossRefPubMedPubMedCentralGoogle Scholar
  233. Wilke CM, Kryczek I, Wei S, Zhao E, Wu K, Wang G et al (2011) Th17 cells in cancer: help or hindrance? Carcinogenesis 32(5):643–649.  https://doi.org/10.1093/carcin/bgr019CrossRefPubMedPubMedCentralGoogle Scholar
  234. Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, Muller-Holzner E et al (2005) The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res 11(23):8326–8331.  https://doi.org/10.1158/1078-0432.CCR-05-1244CrossRefPubMedPubMedCentralGoogle Scholar
  235. Wolfel T, Hauer M, Schneider J, Serrano M, Wolfel C, Klehmann-Hieb E et al (1995) A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269(5228):1281–1284PubMedCrossRefPubMedCentralGoogle Scholar
  236. Wu J, Groh V, Spies T (2002) T cell antigen receptor engagement and specificity in the recognition of stress-inducible MHC class I-related chains by human epithelial gamma delta T cells. J Immunol 169(3):1236–1240PubMedCrossRefPubMedCentralGoogle Scholar
  237. Wu X, Schulte BC, Zhou Y, Haribhai D, Mackinnon AC, Plaza JA et al (2014) Depletion of M2-like tumor-associated macrophages delays cutaneous T-cell lymphoma development in vivo. J Invest Dermatol 134(11):2814–2822.  https://doi.org/10.1038/jid.2014.206CrossRefPubMedPubMedCentralGoogle Scholar
  238. Yamazaki T, Akiba H, Iwai H, Matsuda H, Aoki M, Tanno Y et al (2002) Expression of programmed death 1 ligands by murine T cells and APC. J Immunol 169(10):5538–5545PubMedCrossRefPubMedCentralGoogle Scholar
  239. Yan M, Jene N, Byrne D, Millar EK, O’Toole SA, McNeil CM et al (2011) Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers. Breast Cancer Res 13(2):R47.  https://doi.org/10.1186/bcr2869CrossRefPubMedPubMedCentralGoogle Scholar
  240. Yearley JH, Gibson C, Yu N, Moon C, Murphy E, Juco J et al (2017) PD-L2 expression in human tumors: relevance to anti-PD-1 therapy in cancer. Clin Cancer Res 23(12):3158–3167.  https://doi.org/10.1158/1078-0432.CCR-16-1761CrossRefPubMedPubMedCentralGoogle Scholar
  241. Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tane A, Azuma M, Saito T (2012) Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med 209(6):1201–1217.  https://doi.org/10.1084/jem.20112741CrossRefPubMedPubMedCentralGoogle Scholar
  242. Yotnda P, Firat H, Garcia-Pons F, Garcia Z, Gourru G, Vernant JP et al (1998) Cytotoxic T cell response against the chimeric p210 BCR-ABL protein in patients with chronic myelogenous leukemia. J Clin Invest 101(10):2290–2296PubMedPubMedCentralCrossRefGoogle Scholar
  243. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S et al (2016) Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med 375(9):819–829.  https://doi.org/10.1056/NEJMoa1604958CrossRefPubMedPubMedCentralGoogle Scholar
  244. Zeni E, Mazzetti L, Miotto D, Lo Cascio N, Maestrelli P, Querzoli P et al (2007) Macrophage expression of interleukin-10 is a prognostic factor in nonsmall cell lung cancer. Eur Respir J 30(4):627–632.  https://doi.org/10.1183/09031936.00129306CrossRefPubMedPubMedCentralGoogle Scholar
  245. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G et al (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348(3):203–213PubMedCrossRefPubMedCentralGoogle Scholar
  246. Zhang JP, Yan J, Xu J, Pang XH, Chen MS, Li L et al (2009) Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol 50(5):980–989.  https://doi.org/10.1016/j.jhep.2008.12.033CrossRefPubMedPubMedCentralGoogle Scholar
  247. Zhao J, Huang J, Chen H, Cui L, He W (2006) Vdelta1 T cell receptor binds specifically to MHC I chain related A: molecular and biochemical evidences. Biochem Biophys Res Commun 339(1):232–240PubMedCrossRefPubMedCentralGoogle Scholar
  248. Zheng BJ, Chan KW, Im S, Chua D, Sham JS, Tin PC et al (2001) Anti-tumor effects of human peripheral gammadelta T cells in a mouse tumor model. Int J Cancer 92(3):421–425PubMedCrossRefPubMedCentralGoogle Scholar
  249. Zhu Y, Knolhoff BL, Meyer MA, Nywening TM, West BL, Luo J et al (2014) CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res 74(18):5057–5069.  https://doi.org/10.1158/0008-5472.CAN-13-3723CrossRefPubMedPubMedCentralGoogle Scholar
  250. Zolkind P, Uppaluri R (2017) Checkpoint immunotherapy in head and neck cancers. Cancer Metastasis Rev 36(3):475–489.  https://doi.org/10.1007/s10555-017-9694-9CrossRefPubMedPubMedCentralGoogle Scholar
  251. Zorn E, Hercend T (1999) A natural cytotoxic T cell response in a spontaneously regressing human melanoma targets a neoantigen resulting from a somatic point mutation. Eur J Immunol 29(2):592–601PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Surface Oncology Inc.CambridgeUSA
  2. 2.Department of Basic Medical Sciences, College of Medicine PhoenixUniversity of ArizonaPhoenixUSA

Personalised recommendations