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Immunotherapy in Head and Neck Cancers

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Abstract

Despite tremendous advances in our molecular understanding of carcinogenesis, the worldwide incidence of head and neck squamous cell carcinoma (HNSCC) remains unacceptably high with approximately 664,000 new diagnoses per year. Although roughly one-third of HNSCC patients will reside in developed countries with advanced medical resources, they will be faced with 5-year survival rates that remain quagmired at less than 50 %. Although advances in chemotherapy and radiation continue, cures for HNSCC remain in the surgeon’s purview. Oftentimes surgery leads to disfigurement and the need for adjunctive care for speech, nutrition, and breathing. This chapter will discuss how head and neck cancers avoid immune detection and several novel approaches undergoing clinical evaluation to make them “reappear.” Our discussion will focus on approaches with small molecules, antibodies and antibody drug conjugates (ABCs), and cytokines and a detailed discussion presenting the current and future applications of adoptive (autologous) tumor-specific T-cell therapies and HNSCC tumor vaccines. Abstract and Key Words are contributed by the Editor, AMF.

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References

  1. Mehra R, Cohen RB, Burtness BA. The role of cetuximab for the treatment of squamous cell carcinoma of the head and neck. Clin Adv Hematol Oncol. 2008;6(10):742–50.

    PubMed Central  PubMed  Google Scholar 

  2. Argiris A, et al. Head and neck cancer. Lancet. 2008;371(9625):1695–709.

    Article  PubMed  Google Scholar 

  3. Wong RJ, Shah JP. The role of the head and neck surgeon in contemporary multidisciplinary treatment programs for advanced head and neck cancer. Curr Opin Otolaryngol Head Neck Surg. 2010;18(2):79–82.

    Article  PubMed  Google Scholar 

  4. Pignon JP, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92(1):4–14.

    Article  PubMed  Google Scholar 

  5. Young MR, et al. Mechanisms of immune suppression in patients with head and neck cancer: influence on the immune infiltrate of the cancer. Int J Cancer. 1996;67(3):333–8.

    Article  PubMed  Google Scholar 

  6. Balermpas P, et al. Tumor-infiltrating lymphocytes favor the response to chemoradiotherapy of head and neck cancer. Oncoimmunology. 2014;3(1):e27403.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Pretscher D, et al. Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro- and hypopharyngeal carcinoma. BMC Cancer. 2009;9:292.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Wanebo HJ, et al. T-cell deficiency in patients with squamous cell cancer of the head and neck. Am J Surg. 1975;130(4):445–51.

    Article  PubMed  Google Scholar 

  9. Wang MB, Lichtenstein A, Mickel RA. Hierarchical immunosuppression of regional lymph nodes in patients with head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg. 1991;105(4):517–27.

    PubMed  Google Scholar 

  10. Gillison ML, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92(9):709–20.

    Article  PubMed  Google Scholar 

  11. Lindeberg H, et al. Human papilloma virus (HPV) and carcinomas of the head and neck. Clin Otolaryngol Allied Sci. 1988;13(6):447–54.

    Article  PubMed  Google Scholar 

  12. Loning T, et al. HPV DNA detection in tumours of the head and neck: a comparative light microscopy and DNA hybridization study. ORL J Otorhinolaryngol Relat Spec. 1987;49(5):259–69.

    Article  PubMed  Google Scholar 

  13. Stransky N, et al. The mutational landscape of head and neck squamous cell carcinoma. Science. 2011;333(6046):1157–60.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Koch WM, et al. Head and neck cancer in nonsmokers: a distinct clinical and molecular entity. Laryngoscope. 1999;109(10):1544–51.

    Article  PubMed  Google Scholar 

  15. Wilczynski SP, et al. Detection of human papillomavirus DNA and oncoprotein overexpression are associated with distinct morphological patterns of tonsillar squamous cell carcinoma. Am J Pathol. 1998;152(1):145–56.

    PubMed Central  PubMed  Google Scholar 

  16. King EV, Ottensmeier CH, Thomas GJ. The immune response in HPV oropharyngeal cancer. Oncoimmunology. 2014;3(1):e27254.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Wansom D, et al. Correlation of cellular immunity with human papillomavirus 16 status and outcome in patients with advanced oropharyngeal cancer. Arch Otolaryngol Head Neck Surg. 2010;136(12):1267–73.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Wolchok JD, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122–33.

    Article  PubMed  Google Scholar 

  19. Hodi FS, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Brahmer J, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123–35.

    Article  PubMed  Google Scholar 

  21. Parham P, Janeway C. The immune system. 3rd ed. London/New York: Garland Science; 2009.

    Google Scholar 

  22. Curtsinger JM, et al. Inflammatory cytokines provide a third signal for activation of naive CD4+ and CD8+ T cells. J Immunol. 1999;162(6):3256–62.

    PubMed  Google Scholar 

  23. Valenzuela J, Schmidt C, Mescher M. The roles of IL-12 in providing a third signal for clonal expansion of naive CD8 T cells. J Immunol. 2002;169(12):6842–9.

    Article  PubMed  Google Scholar 

  24. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–64.

    Article  PubMed  Google Scholar 

  25. Powles T, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515(7528):558–62.

    Article  PubMed  Google Scholar 

  26. Iida T, et al. Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4+ T cells. J Immunol. 2000;165(9):5062–8.

    Article  PubMed  Google Scholar 

  27. Guntermann C, Alexander DR. CTLA-4 suppresses proximal TCR signaling in resting human CD4(+) T cells by inhibiting ZAP-70 Tyr(319) phosphorylation: a potential role for tyrosine phosphatases. J Immunol. 2002;168(9):4420–9.

    Article  PubMed  Google Scholar 

  28. van der Merwe PA, et al. CD80 (B7-1) binds both CD28 and CTLA-4 with a low affinity and very fast kinetics. J Exp Med. 1997;185(3):393–403.

    Article  PubMed Central  PubMed  Google Scholar 

  29. Zamarin D, et al. Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci Transl Med. 2014;6(226):226ra32.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Hurwitz AA, et al. CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc Natl Acad Sci U S A. 1998;95(17):10067–71.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271(5256):1734–6.

    Article  PubMed  Google Scholar 

  32. Romano E, et al. Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients. Proc Natl Acad Sci U S A. 2015;112(19):6140–5.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Agata Y, et al. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol. 1996;8(5):765–72.

    Article  PubMed  Google Scholar 

  34. Sheppard KA, et al. PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to PKCtheta. FEBS Lett. 2004;574(1–3):37–41.

    Article  PubMed  Google Scholar 

  35. Yang W, et al. PD-L1: PD-1 interaction contributes to the functional suppression of T-cell responses to human uveal melanoma cells in vitro. Invest Ophthalmol Vis Sci. 2008;49(6):2518–25.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Li B, et al. Anti-programmed death-1 synergizes with granulocyte macrophage colony-stimulating factor--secreting tumor cell immunotherapy providing therapeutic benefit to mice with established tumors. Clin Cancer Res. 2009;15(5):1623–34.

    Article  PubMed  Google Scholar 

  37. Mangsbo SM, et al. Enhanced tumor eradication by combining CTLA-4 or PD-1 blockade with CpG therapy. J Immunother. 2010;33(3):225–35.

    Article  PubMed  Google Scholar 

  38. Nomi T, et al. Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res. 2007;13(7):2151–7.

    Article  PubMed  Google Scholar 

  39. Iwai Y, Terawaki S, Honjo T. PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int Immunol. 2005;17(2):133–44.

    Article  PubMed  Google Scholar 

  40. Curran MA, et al. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A. 2010;107(9):4275–80.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Brahmer JR, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28(19):3167–75.

    Article  PubMed  Google Scholar 

  42. Topalian SL, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Lipson EJ, et al. Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res. 2013;19(2):462–8.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Berger R, et al. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res. 2008;14(10):3044–51.

    Article  PubMed  Google Scholar 

  45. Hamid O, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369(2):134–44.

    Article  PubMed Central  PubMed  Google Scholar 

  46. Larkin J, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(1):23–34.

    Article  PubMed  Google Scholar 

  47. Callahan MK, Wolchok JD. At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy. J Leukoc Biol. 2013;94(1):41–53.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Herbst RS, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563–7.

    Article  PubMed  Google Scholar 

  49. Freeman GJ, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Chen J, et al. Interferon-gamma-induced PD-L1 surface expression on human oral squamous carcinoma via PKD2 signal pathway. Immunobiology. 2012;217(4):385–93.

    Article  PubMed  Google Scholar 

  51. Muhlbauer M, et al. PD-L1 is induced in hepatocytes by viral infection and by interferon-alpha and -gamma and mediates T cell apoptosis. J Hepatol. 2006;45(4):520–8.

    Article  PubMed  Google Scholar 

  52. Terawaki S, et al. IFN-alpha directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity. J Immunol. 2011;186(5):2772–9.

    Article  PubMed  Google Scholar 

  53. Akbay EA, et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 2013;3(12):1355–63.

    Article  PubMed  Google Scholar 

  54. Herbst RS, Gordon MS, Gregg Daniel F, Jeffrey Alan S, Jean-Charles S, Omid H, Powderly JD, Burris HA, Ahmad M, Marcin K, Maya L, Maria A, Chen DS, Stephen Hodi F. A study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors. J Clin Oncol (Meeting Abstracts). 2013;31(15_suppl 3000).

    Google Scholar 

  55. Brahmer JR, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–65.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Emens LA, Braiteh FS, Philippe C, Jean-Pierre D, Joseph PE, Marcella F, Yuanyuan X, Yan W, Luciana M, Chen DS, Ian K. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer (TNBC). Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015. Abstract #2859.

    Google Scholar 

  57. Spira AI, Keunchil P, Julien M, Vansteenkiste JF, Achim R, Marcus B, Daniel W, Marcin K, Ahmad M, Louis F. Efficacy, safety and predictive biomarker results from a randomized phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POPLAR). J Clin Oncol. 2015;33(Suppl; abstr 8010).

    Google Scholar 

  58. Galon J, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.

    Article  PubMed  Google Scholar 

  59. Dudley ME, et al. Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunother. 2003;26(4):332–42.

    Article  PubMed Central  PubMed  Google Scholar 

  60. Wu R, et al. Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes for metastatic melanoma: current status and future outlook. Cancer J. 2012;18(2):160–75.

    Article  PubMed Central  PubMed  Google Scholar 

  61. LaCelle MG, Jensen SM, Fox BA. Partial CD4 depletion reduces regulatory T cells induced by multiple vaccinations and restores therapeutic efficacy. Clin Cancer Res. 2009;15(22):6881–90.

    Article  PubMed Central  PubMed  Google Scholar 

  62. Valzasina B, et al. Triggering of OX40 (CD134) on CD4(+)CD25+ T cells blocks their inhibitory activity: a novel regulatory role for OX40 and its comparison with GITR. Blood. 2005;105(7):2845–51.

    Article  PubMed  Google Scholar 

  63. Weinberg AD, et al. Science gone translational: the OX40 agonist story. Immunol Rev. 2011;244(1):218–31.

    Article  PubMed Central  PubMed  Google Scholar 

  64. Woo EY, et al. Cutting edge: regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J Immunol. 2002;168(9):4272–6.

    Article  PubMed  Google Scholar 

  65. Dudley ME. Adoptive cell therapy for patients with melanoma. J Cancer Educ. 2011;2:360–2.

    Article  Google Scholar 

  66. Rosenberg SA, et al. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer. 2008;8(4):299–308.

    Article  PubMed Central  PubMed  Google Scholar 

  67. Rosenberg SA, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17(13):4550–7.

    Article  PubMed Central  PubMed  Google Scholar 

  68. Ohtani T, et al. Activated cytotoxic T-lymphocyte immunotherapy is effective for advanced oral and maxillofacial cancers. Int J Oncol. 2014;45(5):2051–7.

    PubMed  Google Scholar 

  69. Yannelli JR, et al. Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience. Int J Cancer. 1996;65(4):413–21.

    Article  PubMed  Google Scholar 

  70. Dudley ME, et al. Randomized selection design trial evaluating CD8 + -enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma. J Clin Oncol. 2013;31(17):2152–9.

    Article  PubMed Central  PubMed  Google Scholar 

  71. Junker N, et al. Bimodal ex vivo expansion of T cells from patients with head and neck squamous cell carcinoma: a prerequisite for adoptive cell transfer. Cytotherapy. 2011;13(7):822–34.

    Article  PubMed  Google Scholar 

  72. Chacon JA, et al. Manipulating the tumor microenvironment ex vivo for enhanced expansion of tumor-infiltrating lymphocytes for adoptive cell therapy. Clin Cancer Res. 2015;21(3):611–21.

    Article  PubMed Central  PubMed  Google Scholar 

  73. Rosenberg SA, et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med. 1987;316(15):889–97.

    Article  PubMed  Google Scholar 

  74. Mocellin S, et al. Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis. J Natl Cancer Inst. 2010;102(7):493–501.

    Article  PubMed  Google Scholar 

  75. Malek TR. The biology of interleukin-2. Annu Rev Immunol. 2008;26:453–79.

    Article  PubMed  Google Scholar 

  76. Scheffold A, Huhn J, Hofer T. Regulation of CD4 + CD25+ regulatory T cell activity: it takes (IL-)two to tango. Eur J Immunol. 2005;35(5):1336–41.

    Article  PubMed  Google Scholar 

  77. Atkins MB, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17(7):2105–16.

    PubMed  Google Scholar 

  78. Fisher RI, Rosenberg SA, Fyfe G. Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am. 2000;6 Suppl 1:S55–7.

    PubMed  Google Scholar 

  79. Klapper JA, et al. 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. 2008;113(2):293–301.

    Article  PubMed Central  PubMed  Google Scholar 

  80. Payne R, et al. Durable responses and reversible toxicity of high-dose interleukin-2 treatment of melanoma and renal cancer in a Community Hospital Biotherapy Program. J Immunother Cancer. 2014;2:13.

    Article  PubMed Central  PubMed  Google Scholar 

  81. Atkins MB, et al. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am. 2000;6 Suppl 1:S11–4.

    PubMed  Google Scholar 

  82. Wanebo HJ, et al. Immune restoration with interleukin-2 in patients with squamous cell carcinoma of the head and neck. Am J Surg. 1989;158(4):356–60.

    Article  PubMed  Google Scholar 

  83. Cortesina G, et al. The effect of preoperative local interleukin-2 (IL-2) injections in patients with head and neck squamous cell carcinoma. An immunological study. Acta Otolaryngol. 1991;111(2):428–33.

    Article  PubMed  Google Scholar 

  84. Cortesina G, et al. Temporary regression of recurrent squamous cell carcinoma of the head and neck is achieved with a low but not with a high dose of recombinant interleukin 2 injected perilymphatically. Br J Cancer. 1994;69(3):572–6.

    Article  PubMed Central  PubMed  Google Scholar 

  85. Cortesina G, et al. Interleukin-2 injected around tumor-draining lymph nodes in head and neck cancer. Head Neck. 1991;13(2):125–31.

    Article  PubMed  Google Scholar 

  86. De Stefani A, et al. Treatment of oral cavity and oropharynx squamous cell carcinoma with perilymphatic interleukin-2: clinical and pathologic correlations. J Immunother Emphasis Tumor Immunol. 1996;19(2):125–33.

    Article  PubMed  Google Scholar 

  87. Saito T, et al. Clinical evaluation of local administration of RIL-2 in head and neck cancer. Nihon Jibiinkoka Gakkai Kaiho. 1989;92(8):1265–70.

    Article  PubMed  Google Scholar 

  88. Wei S, et al. Interleukin-2 administration alters the CD4+FOXP3+ T-cell pool and tumor trafficking in patients with ovarian carcinoma. Cancer Res. 2007;67(15):7487–94.

    Article  PubMed  Google Scholar 

  89. Belardelli F, et al. Interferon-alpha in tumor immunity and immunotherapy. Cytokine Growth Factor Rev. 2002;13(2):119–34.

    Article  PubMed  Google Scholar 

  90. Trinchieri G. Type I interferon: friend or foe? J Exp Med. 2010;207(10):2053–63.

    Article  PubMed Central  PubMed  Google Scholar 

  91. van Herpen CM, et al. Intratumoral recombinant human interleukin-12 administration in head and neck squamous cell carcinoma patients modifies locoregional lymph node architecture and induces natural killer cell infiltration in the primary tumor. Clin Cancer Res. 2005;11(5):1899–909.

    Article  PubMed  Google Scholar 

  92. van Herpen CM, et al. Intratumoral rhIL-12 administration in head and neck squamous cell carcinoma patients induces B cell activation. Int J Cancer. 2008;123(10):2354–61.

    Article  PubMed  Google Scholar 

  93. Piconese S, Valzasina B, Colombo MP. OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection. J Exp Med. 2008;205(4):825–39.

    Article  PubMed Central  PubMed  Google Scholar 

  94. Jensen SM, et al. Signaling through OX40 enhances antitumor immunity. Semin Oncol. 2010;37(5):524–32.

    Article  PubMed Central  PubMed  Google Scholar 

  95. Curti BD, et al. OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res. 2013;73(24):7189–98.

    Article  PubMed Central  PubMed  Google Scholar 

  96. Futagawa T, et al. Expression and function of 4-1BB and 4-1BB ligand on murine dendritic cells. Int Immunol. 2002;14(3):275–86.

    Article  PubMed  Google Scholar 

  97. Cheuk AT, Mufti GJ, Guinn BA. Role of 4-1BB:4-1BB ligand in cancer immunotherapy. Cancer Gene Ther. 2004;11(3):215–26.

    Article  PubMed  Google Scholar 

  98. Mittler RS, et al. Anti-4-1BB monoclonal antibodies abrogate T cell-dependent humoral immune responses in vivo through the induction of helper T cell anergy. J Exp Med. 1999;190(10):1535–40.

    Article  PubMed Central  PubMed  Google Scholar 

  99. Foell J, et al. CD137 costimulatory T cell receptor engagement reverses acute disease in lupus-prone NZB x NZW F1 mice. J Clin Invest. 2003;111(10):1505–18.

    Article  PubMed Central  PubMed  Google Scholar 

  100. Chen S, et al. Combination of 4-1BB agonist and PD-1 antagonist promotes antitumor effector/memory CD8 T cells in a poorly immunogenic tumor model. Cancer Immunol Res. 2015;3(2):149–60.

    Article  PubMed  Google Scholar 

  101. Vinay DS, Kwon BS. Immunotherapy of cancer with 4-1BB. Mol Cancer Ther. 2012;11(5):1062–70.

    Article  PubMed  Google Scholar 

  102. Bajor DL, Rosemarie M, Riese MJ, Richman LP, Xu X, Torigian DA, Stelekati E, Sweeney M, Sullivan B, Schuchter LM, Amaravadi R, John Wherry E, Vonderheide RH. Combination of agonistic CD40 monoclonal antibody CP-870,893 and anti-CTLA-4 antibody tremelimumab in patients with metastatic melanoma. Proceedings of the 106th Annual Meeting of the American Association for Cancer Research, Philadelphia; 2015.

    Google Scholar 

  103. Hu X, et al. Enhancement of cytolytic T lymphocyte precursor frequency in melanoma patients following immunization with the MAGE-1 peptide loaded antigen presenting cell-based vaccine. Cancer Res. 1996;56(11):2479–83.

    PubMed  Google Scholar 

  104. Barve M, et al. Induction of immune responses and clinical efficacy in a phase II trial of IDM-2101, a 10-epitope cytotoxic T-lymphocyte vaccine, in metastatic non-small-cell lung cancer. J Clin Oncol. 2008;26(27):4418–25.

    Article  PubMed  Google Scholar 

  105. Schwartzentruber DJ, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011;364(22):2119–27.

    Article  PubMed Central  PubMed  Google Scholar 

  106. Kantoff PW, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–22.

    Article  PubMed  Google Scholar 

  107. Aris M, et al. MART-1- and gp100-expressing and -non-expressing melanoma cells are equally proliferative in tumors and clonogenic in vitro. J Invest Dermatol. 2012;132(2):365–74.

    Article  PubMed  Google Scholar 

  108. Dranoff G. GM-CSF-based cancer vaccines. Immunol Rev. 2002;188:147–54.

    Article  PubMed  Google Scholar 

  109. Srivatsan S, et al. Allogeneic tumor cell vaccines: the promise and limitations in clinical trials. Hum Vaccin Immunother. 2014;10(1):52–63.

    Article  PubMed Central  PubMed  Google Scholar 

  110. Lutz E, et al. A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A Phase II trial of safety, efficacy, and immune activation. Ann Surg. 2011;253(2):328–35.

    Article  PubMed Central  PubMed  Google Scholar 

  111. Levine B. Unraveling the role of autophagy in cancer. Autophagy. 2006;2(2):65–6.

    Article  PubMed  Google Scholar 

  112. Eskelinen EL. The dual role of autophagy in cancer. Curr Opin Pharmacol. 2011;11(4):294–300.

    Article  PubMed  Google Scholar 

  113. Mathew R, Karantza-Wadsworth V, White E. Role of autophagy in cancer. Nat Rev Cancer. 2007;7(12):961–7.

    Article  PubMed Central  PubMed  Google Scholar 

  114. Li Y, et al. Efficient cross-presentation depends on autophagy in tumor cells. Cancer Res. 2008;68(17):6889–95.

    Article  PubMed Central  PubMed  Google Scholar 

  115. Li Y, et al. Cross-presentation of tumor associated antigens through tumor-derived autophagosomes. Autophagy. 2009;5(4):576–7.

    Article  PubMed Central  PubMed  Google Scholar 

  116. Dolan BP, et al. Distinct pathways generate peptides from defective ribosomal products for CD8+ T cell immunosurveillance. J Immunol. 2011;186(4):2065–72.

    Article  PubMed Central  PubMed  Google Scholar 

  117. Yewdell JW, Anton LC, Bennink JR. Defective ribosomal products (DRiPs): a major source of antigenic peptides for MHC class I molecules? J Immunol. 1996;157(5):1823–6.

    PubMed  Google Scholar 

  118. Twitty CG, et al. Tumor-derived autophagosome vaccine: induction of cross-protective immune responses against short-lived proteins through a p62-dependent mechanism. Clin Cancer Res. 2011;17(20):6467–81.

    Article  PubMed Central  PubMed  Google Scholar 

  119. Li Y, et al. Tumor-derived autophagosome vaccine: mechanism of cross-presentation and therapeutic efficacy. Clin Cancer Res. 2011;17(22):7047–57.

    Article  PubMed Central  PubMed  Google Scholar 

  120. Chaturvedi A, Engels E, Anderson W, Gillison M. Incidence trends for human papillomavirus-related (HPV-R) and unrelated (HPV-U) head and neck squamous cell carcinomas (HNSCC) in the United States (US). J Clin Oncol (Meeting Abstracts), 2007;25(no. 18_suppl 6001).

    Google Scholar 

  121. Chaturvedi AK. Epidemiology and clinical aspects of HPV in head and neck cancers. Head Neck Pathol. 2012;6 Suppl 1:S16–24.

    Article  PubMed  Google Scholar 

  122. Paavonen J, et al. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet. 2007;369(9580):2161–70.

    Article  PubMed  Google Scholar 

  123. Villa LL, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer. 2006;95(11):1459–66.

    Article  PubMed Central  PubMed  Google Scholar 

  124. Rizvi NA, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124–8.

    Article  PubMed  Google Scholar 

  125. Tumeh PC, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71.

    Article  PubMed Central  PubMed  Google Scholar 

  126. Cross M. ERG oncoprotein overexpression in prostate cancer. Multiplex IHC adds to diagnostic prowess and efficiency of laboratory. MLO Med Lab Obs. 2011;43(7):22. 42.

    PubMed  Google Scholar 

  127. Stack EC, et al. Multiplexed immunohistochemistry, imaging, and quantitation: a review, with an assessment of Tyramide signal amplification, multispectral imaging and multiplex analysis. Methods. 2014;70(1):46–58.

    Article  PubMed  Google Scholar 

  128. Feng Z, et al. Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor-infiltrating lymphocytes from melanoma. J. Immunother Cancer. 2015;3:47.

    Google Scholar 

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Authors and Affiliations

  1. Laboratory of Molecular and Tumor Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Providence Portland Medical Center, 4805 NE Glisan St, Portland, OR, 97213, USA

    Zipei Feng BS, MD, PhD & Bernard A. Fox PhD

  2. Departments of Cancer Biology, Oregon Health & Science University, Portland, OR, USA

    Zipei Feng BS, MD, PhD

  3. Providence Portland Regional Laboratory, Portland, OR, USA

    Carlo B. Bifulco MD

  4. Department of Translational Molecular Pathology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Cancer Center, Providence Portland Medical Center, 4805 NE Glisan St, Portland, OR, 97213, USA

    Carlo B. Bifulco MD

  5. Providence Oral, Head and Neck Cancer Program, Providence Portland Medical Center, Providence Cancer Center, Robert W. Franz Research Cancer Center, Earle A. Chiles Research Institute, 4805 NE Glisan Street, 2N35, Portland, OR, 97213, USA

    Rom Leidner MD

  6. Department of Surgery, Providence Oral, Head and Neck Cancer Program, Providence Portland Medical Center, Providence Cancer Center, Robert W. Franz Research Cancer Center, Earle A. Chiles Research Institute, 4805 NE Glisan Street, 2N35, Portland, OR, 97213, USA

    R. Bryan Bell MD, DDS, FACS

  7. Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR,, USA

    Bernard A. Fox PhD

  8. UbiVac, Portland, OR, USA

    Bernard A. Fox PhD

Authors
  1. Zipei Feng BS, MD, PhD
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  2. Carlo B. Bifulco MD
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  3. Rom Leidner MD
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  4. R. Bryan Bell MD, DDS, FACS
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  5. Bernard A. Fox PhD
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Corresponding author

Correspondence to Zipei Feng BS, MD, PhD .

Editor information

Editors and Affiliations

  1. School of Medicine, Wayne State University, DETROIT, Michigan, USA

    Andrew M. Fribley

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Feng, Z., Bifulco, C.B., Leidner, R., Bell, R.B., Fox, B.A. (2016). Immunotherapy in Head and Neck Cancers. In: M. Fribley, A. (eds) Targeting Oral Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-27647-2_9

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  • DOI: https://doi.org/10.1007/978-3-319-27647-2_9

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