Skip to main content
SpringerLink
Log in

Immunopathology as a Basis for Immunotherapy of Head and Neck Squamous Cell Carcinoma

  • Chapter
  • First Online:
Cancer Immunology

  • 804 Accesses

Abstract

Immunologic strategies to treat head and neck squamous cell carcinoma (HNSCC) have recently attracted new interest with the introduction of immunotherapy like checkpoint inhibitors into the clinical routine. Simultaneously, therapy-related resistance has also been observed. The immunologic features of HNSCC, which is highly immune suppressive, have been characterized and recently, the immune suppression and invasion of HNSCC-cancer stem cells have been recognized. This chapter discusses current findings of the immunopathology of HNSCC with regard to the development of immunotherapies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29. https://doi.org/10.3322/caac.21208.

    Article  PubMed  Google Scholar 

  2. Bottley G, Watherston OG, Hiew YL, et al. High- risk human papillomavirus E7 expression reduces cellsurface MHC class I molecules and increases susceptibility to natural killer cells. Oncogene 2008;27:1794–9.

    Google Scholar 

  3. Guirat-Dhouib N, Baccar Y, Mustapha IB, Ouederni M, Chouaibi S, El Fekih N, Barbouche MR, Fezaa B, Kouki R, Hmida S, Mellouli F, Bejaoui M. Oral HPV infection and MHC class II deficiency (A study of two cases with atypical outcome). Clinical and Molecular Allergy 2012;10(6). https://doi.org/10.1186/1476-7961-10-6.

  4. Leemans CR, Braakhuis BJ, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011;11(1):9–22. Epub 2010/12/17. https://doi.org/10.1038/nrc2982.

    Article  CAS  PubMed  Google Scholar 

  5. Cancer Genome Atlas N. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature. 2015;517(7536):576–82. https://doi.org/10.1038/nature14129. PubMed PMID: 25631445; PubMed Central PMCID: PMCPMC4311405

    Article  CAS  Google Scholar 

  6. Coordes A, Lenz K, Qian X, Lenarz M, Kaufmann AM, Albers AE. Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status. Eur Arch Otorhinolaryngol. 2016;273(8):2157–69. https://doi.org/10.1007/s00405-015-3728-0.

    Article  PubMed  Google Scholar 

  7. Qian X, Kaufmann AM, Chen C, Tzamalis G, Hofmann VM, Keilholz U, et al. Prevalence and associated survival of high-risk HPV-related adenoid cystic carcinoma of the salivary glands. Int J Oncol. 2016;49(2):803–11. https://doi.org/10.3892/ijo.2016.3563.

    Article  CAS  PubMed  Google Scholar 

  8. Lydiatt WM, Patel SG, O'Sullivan B, Brandwein MS, Ridge JA, Migliacci JC, et al. Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(2):122–37. https://doi.org/10.3322/caac.21389.

    Article  PubMed  Google Scholar 

  9. Gillison ML, Zhang Q, Jordan R, Xiao W, Westra WH, Trotti A, et al. Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol. 2012;30(17):2102–11. https://doi.org/10.1200/JCO.2011.38.4099. PubMed PMID: 22565003; PubMed Central PMCID: PMCPMC3397696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Anantharaman D, Muller DC, Lagiou P, Ahrens W, Holcatova I, Merletti F, et al. Combined effects of smoking and HPV16 in oropharyngeal cancer. Int J Epidemiol. 2016;45(3):752–61. https://doi.org/10.1093/ije/dyw069.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Chaturvedi AK, D'Souza G, Gillison ML, Katki HA. Burden of HPV-positive oropharynx cancers among ever and never smokers in the U.S. population. Oral Oncol. 2016;60:61–7. https://doi.org/10.1016/j.oraloncology.2016.06.006.

    Article  PubMed  Google Scholar 

  12. Hoffmann TK, Bier H, Donnenberg AD, Whiteside TL, De Leo AB. p53 as an immunotherapeutic target in head and neck cancer. Adv Otorhinolaryngol. 2005;62:151–60. https://doi.org/10.1159/000082505.

    Article  CAS  PubMed  Google Scholar 

  13. Adelstein D, Gillison ML, Pfister DG, Spencer S, Adkins D, Brizel DM, et al. NCCN Guidelines Insights: head and neck cancers, Version 2.2017. J Natl Compr Cancer Netw. 2017;15(6):761–70. https://doi.org/10.6004/jnccn.2017.0101.

    Article  CAS  Google Scholar 

  14. Albers AE, Chen C, Koberle B, Qian X, Klussmann JP, Wollenberg B, et al. Stem cells in squamous head and neck cancer. Crit Rev Oncol Hematol. 2012;81(3):224–40. Epub 2011/04/23. https://doi.org/10.1016/j.critrevonc.2011.03.004.

    Article  PubMed  Google Scholar 

  15. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3(11):991–8. https://doi.org/10.1038/ni1102-991.

    Article  CAS  PubMed  Google Scholar 

  16. Albers AE, Ferris RL, Kim GG, Chikamatsu K, DeLeo AB, Whiteside TL. Immune responses to p53 in patients with cancer: enrichment in tetramer+ p53 peptide-specific T-cells and regulatory T-cells at tumor sites. Cancer Immunol immunother: CII. 2005;54(11):1072–81. Epub 2005/06/17. https://doi.org/10.1007/s00262-005-0670-9.

    Article  CAS  PubMed  Google Scholar 

  17. Albers AE, Schaefer C, Visus C, Gooding W, DeLeo AB, Whiteside TL. Spontaneous apoptosis of tumor-specific tetramer+ CD8+ T lymphocytes in the peripheral circulation of patients with head and neck cancer. Head Neck. 2009;31(6):773–81. Epub 2009/03/20. https://doi.org/10.1002/hed.21031.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Albers AE, Visus C, Tsukishiro T, Ferris RL, Gooding W, Whiteside TL, et al. Alterations in the T-cell receptor variable beta gene-restricted profile of CD8+ T lymphocytes in the peripheral circulation of patients with squamous cell carcinoma of the head and neck. Clin Cancer Res. 2006;12(8):2394–403. Epub 2006/04/28. https://doi.org/10.1158/1078-0432.CCR-05-1818.

    Article  CAS  PubMed  Google Scholar 

  19. Hoffmann TK, Dworacki G, Tsukihiro T, Meidenbauer N, Gooding W, Johnson JT, et al. Spontaneous apoptosis of circulating T lymphocytes in patients with head and neck cancer and its clinical importance. Clin Cancer Res. 2002;8(8):2553–62. Epub 2002/08/13

    PubMed  Google Scholar 

  20. Chikamatsu K, Albers A, Stanson J, Kwok WW, Appella E, Whiteside TL, et al. P53(110-124)-specific human CD4+ T-helper cells enhance in vitro generation and antitumor function of tumor-reactive CD8+ T-cells. Cancer Res. 2003;63(13):3675–81. Epub 2003/07/04

    CAS  PubMed  Google Scholar 

  21. Whiteside TL, Schuler P, Schilling B. Induced and natural regulatory T-cells in human cancer. Expert Opin Biol Ther. 2012;12(10):1383–97. Epub 2012/08/02. https://doi.org/10.1517/14712598.2012.707184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lanzavecchia A, Sallusto F. Progressive differentiation and selection of the fittest in the immune response. Nat Rev Immunol. 2002;2(12):982–7. Epub 2002/12/04. https://doi.org/10.1038/nri959.

    Article  CAS  PubMed  Google Scholar 

  23. Czystowska M, Gooding W, Szczepanski MJ, Lopez-Abaitero A, Ferris RL, Johnson JT, et al. The immune signature of CD8(+)CCR7(+) T-cells in the peripheral circulation associates with disease recurrence in patients with HNSCC. Clin Cancer Res. 2013;19(4):889–99. Epub 2013/02/01. https://doi.org/10.1158/1078-0432.CCR-12-2191.

    Article  CAS  PubMed  Google Scholar 

  24. Watanabe M, Kono K, Kawaguchi Y, Mizukami Y, Mimura K, Maruyama T, et al. Interleukin-21 can efficiently restore impaired antibody-dependenT-cell-mediated cytotoxicity in patients with oesophageal squamous cell carcinoma. Br J Cancer. 2010;102(3):520–9. https://doi.org/10.1038/sj.bjc.6605502. Epub 2009/12/24. PubMed PMID: 20029417; PubMed Central PMCID: PMC2822939

    Article  CAS  PubMed  Google Scholar 

  25. Ferris RL, Jaffee EM, Ferrone S. Tumor antigen-targeted, monoclonal antibody-based immunotherapy: clinical response, cellular immunity, and immunoescape. J Clin Oncol. 2010;28(28):4390–9. https://doi.org/10.1200/JCO.2009.27.6360. PubMed PMID: 20697078; PubMed Central PMCID: PMCPMC2954137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chikamatsu K, Nakano K, Storkus WJ, Appella E, Lotze MT, Whiteside TL, et al. Generation of anti-p53 cytotoxic T lymphocytes from human peripheral blood using autologous dendritic cells. Clin Cancer Res. 1999;5(6):1281–8. Epub 1999/07/02

    CAS  PubMed  Google Scholar 

  27. Soussi T. The humoral response to the tumor-suppressor gene-product p53 in human cancer: implications for diagnosis and therapy. Immunol Today. 1996;17(8):354–6. Epub 1996/08/01. https://doi.org/10.1016/0167-5699(96)30019-4.

    Article  CAS  PubMed  Google Scholar 

  28. Hoffmann TK, Nakano K, Elder EM, Dworacki G, Finkelstein SD, Appella E, et al. Generation of T-cells specific for the wild-type sequence p53(264–272) peptide in cancer patients: implications for immunoselection of epitope loss variants. J Immunol. 2000;165(10):5938–44. Epub 2000/11/09

    Article  CAS  PubMed  Google Scholar 

  29. Schaefer C, Kim GG, Albers A, Hoermann K, Myers EN, Whiteside TL. Characteristics of CD4+CD25+ regulatory T-cells in the peripheral circulation of patients with head and neck cancer. Br J Cancer. 2005;92(5):913–20. https://doi.org/10.1038/sj.bjc.6602407. Epub 2005/02/17. PubMed PMID: 15714205; PubMed Central PMCID: PMC2361917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Shimizu J, Yamazaki S, Sakaguchi S. Induction of tumor immunity by removing CD25+CD4+ T-cells: a common basis between tumor immunity and autoimmunity. J Immunol. 1999;163(10):5211–8. Epub 1999/11/24

    CAS  PubMed  Google Scholar 

  31. Kuss I, Donnenberg AD, Gooding W, Whiteside TL. Effector CD8+CD45RO-CD27-T-cells have signalling defects in patients with squamous cell carcinoma of the head and neck. Br J Cancer. 2003;88(2):223–30. https://doi.org/10.1038/sj.bjc.6600694. Epub 2003/03/01. PubMed PMID: 12610507; PubMed Central PMCID: PMC2377049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H. The central role of CD4(+) T-cells in the antitumor immune response. J Exp Med. 1998;188(12):2357–68. Epub 1998/12/22. PubMed PMID: 9858522; PubMed Central PMCID: PMC2212434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Knutson KL, Disis ML. Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother. 2005;54(8):721–8. Epub 2005/07/13. https://doi.org/10.1007/s00262-004-0653-2.

    Article  CAS  PubMed  Google Scholar 

  34. Chikamatsu K, Sakakura K, Yamamoto T, Furuya N, Whiteside TL, Masuyama K. CD4+ T helper responses in squamous cell carcinoma of the head and neck. Oral Oncol. 2008;44(9):870–7. Epub 2008/01/29. https://doi.org/10.1016/j.oraloncology.2007.11.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ito D, Albers A, Zhao YX, Visus C, Appella E, Whiteside TL, et al. The wild-type sequence (wt) p53(25-35) peptide induces HLA-DR7 and HLA-DR11-restricted CD4+ Th cells capable of enhancing the ex vivo expansion and function of anti-wt p53(264-272) peptide CD8+ T-cells. J Immunol. 2006;177(10):6795–803. Epub 2006/11/04

    Article  CAS  PubMed  Google Scholar 

  36. Chikamatsu K, Sakakura K, Takahashi G, Okamoto A, Furuya N, Whiteside TL, et al. CD4+ T-cell responses to HLA-DP5-restricted wild-type sequence p53 peptides in patients with head and neck cancer. Cancer Immunol Immunother. 2009;58(9):1441–8. Epub 2009/02/03. https://doi.org/10.1007/s00262-009-0661-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bhat P, Mattarollo SR, Gosmann C, Frazer IH, Leggatt GR. Regulation of immune responses to HPV infection and during HPV-directed immunotherapy. Immunol Rev. 2011;239(1):85–98. Epub 2011/01/05. https://doi.org/10.1111/j.1600-065X.2010.00966.x.

    Article  CAS  PubMed  Google Scholar 

  38. Hoffmann TK, Loftus DJ, Nakano K, Maeurer MJ, Chikamatsu K, Appella E, et al. The ability of variant peptides to reverse the nonresponsiveness of T lymphocytes to the wild-type sequence p53(264-272) epitope. J Immunol. 2002;168(3):1338–47. Epub 2002/01/22

    Article  CAS  PubMed  Google Scholar 

  39. Albers A, Abe K, Hunt J, Wang J, Lopez-Albaitero A, Schaefer C, et al. Antitumor activity of human papillomavirus type 16 E7-specific T-cells against virally infected squamous cell carcinoma of the head and neck. Cancer Res. 2005;65(23):11146–55. Epub 2005/12/03. https://doi.org/10.1158/0008-5472.CAN-05-0772.

    Article  CAS  PubMed  Google Scholar 

  40. Williams R, Lee DW, Elzey BD, Anderson ME, Hostager BS, Lee JH. Preclinical models of HPV+ and HPV- HNSCC in mice: an immune clearance of HPV+ HNSCC. Head Neck. 2009;31(7):911–8. Epub 2009/03/14. https://doi.org/10.1002/hed.21040.

    Article  PubMed  Google Scholar 

  41. Taylor GS, Jia H, Harrington K, Lee LW, Turner J, Ladell K, et al. A recombinant modified vaccinia ankara vaccine encoding Epstein-Barr Virus (EBV) target antigens: a phase I trial in UK patients with EBV-positive cancer. Clin Cancer Res. 2014;20(19):5009–22. https://doi.org/10.1158/1078-0432.CCR-14-1122-T. PubMed PMID: 25124688; PubMed Central PMCID: PMCPMC4340506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Whiteside TL. Tumor-induced death of immune cells: its mechanisms and consequences. Semin Cancer Biol. 2002;12(1):43–50. Epub 2002/04/03. https://doi.org/10.1006/scbi.2001.0402.

    Article  CAS  PubMed  Google Scholar 

  43. Kuss I, Hathaway B, Ferris RL, Gooding W, Whiteside TL. Decreased absolute counts of T lymphocyte subsets and their relation to disease in squamous cell carcinoma of the head and neck. Clin Cancer Res. 2004;10(11):3755–62. Epub 2004/06/03. https://doi.org/10.1158/1078-0432.CCR-04-0054.

    Article  CAS  PubMed  Google Scholar 

  44. Kuss I, Hathaway B, Ferris RL, Gooding W, Whiteside TL. Imbalance in absolute counts of T lymphocyte subsets in patients with head and neck cancer and its relation to disease. Adv Otorhinolaryngol. 2005;62:161–72. Epub 2004/12/21. https://doi.org/10.1159/000082506.

    Article  CAS  PubMed  Google Scholar 

  45. Tsukishiro T, Donnenberg AD, Whiteside TL. Rapid turnover of the CD8(+)CD28(−) T-cell subset of effector cells in the circulation of patients with head and neck cancer. Cancer Immunol Immunother. 2003;52(10):599–607. Epub 2003/06/27. https://doi.org/10.1007/s00262-003-0395-6.

    Article  PubMed  Google Scholar 

  46. Reichert TE, Strauss L, Wagner EM, Gooding W, Whiteside TL. Signaling abnormalities, apoptosis, and reduced proliferation of circulating and tumor-infiltrating lymphocytes in patients with oral carcinoma. Clin Cancer Res. 2002;8(10):3137–45. Epub 2002/10/11

    PubMed  Google Scholar 

  47. Strauss L, Bergmann C, Whiteside TL. Human circulating CD4+CD25highFoxp3+ regulatory T-cells kill autologous CD8+ but not CD4+ responder cells by Fas-mediated apoptosis. J Immunol. 2009;182(3):1469–80. Epub 2009/01/22

    Article  CAS  PubMed  Google Scholar 

  48. Whiteside TL. Signaling defects in T lymphocytes of patients with malignancy. Cancer Immunol Immunother. 1999;48(7):346–52. Epub 1999/09/29

    Article  CAS  PubMed  Google Scholar 

  49. Reichert TE, Day R, Wagner EM, Whiteside TL. Absent or low expression of the zeta chain in T-cells at the tumor site correlates with poor survival in patients with oral carcinoma. Cancer Res. 1998;58(23):5344–7. Epub 1998/12/16

    CAS  PubMed  Google Scholar 

  50. Okada K, Komuta K, Hashimoto S, Matsuzaki S, Kanematsu T, Koji T. Frequency of apoptosis of tumor-infiltrating lymphocytes induced by fas counterattack in human colorectal carcinoma and its correlation with prognosis. Clin Cancer Res. 2000;6(9):3560–4. Epub 2000/09/22

    CAS  PubMed  Google Scholar 

  51. Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY. A function for interleukin 2 in Foxp3-expressing regulatory T-cells. Nat Immunol. 2005;6(11):1142–51. Epub 2005/10/18. https://doi.org/10.1038/ni1263.

    Article  CAS  PubMed  Google Scholar 

  52. Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, et al. Prevalence of regulatory T-cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol. 2002;169(5):2756–61. Epub 2002/08/24

    Article  CAS  PubMed  Google Scholar 

  53. Strauss L, Bergmann C, Gooding W, Johnson JT, Whiteside TL. The frequency and suppressor function of CD4+CD25highFoxp3+ T-cells in the circulation of patients with squamous cell carcinoma of the head and neck. Clin Cancer Res. 2007;13(21):6301–11. Epub 2007/11/03. https://doi.org/10.1158/1078-0432.CCR-07-1403.

    Article  CAS  PubMed  Google Scholar 

  54. Strauss L, Bergmann C, Szczepanski M, Gooding W, Johnson JT, Whiteside TL. A unique subset of CD4+CD25highFoxp3+ T-cells secreting interleukin-10 and transforming growth factor-beta1 mediates suppression in the tumor microenvironment. Clin Cancer Res. 2007;13(15 Pt 1):4345–54. Epub 2007/08/03. https://doi.org/10.1158/1078-0432.CCR-07-0472.

    Article  CAS  PubMed  Google Scholar 

  55. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, et al. Specific recruitment of regulatory T-cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10(9):942–9. Epub 2004/08/24. https://doi.org/10.1038/nm1093.

    Article  CAS  PubMed  Google Scholar 

  56. Boucek J, Mrkvan T, Chovanec M, Kuchar M, Betka J, Boucek V, et al. Regulatory T-cells and their prognostic value for patients with squamous cell carcinoma of the head and neck. J Cell Mol Med. 2010;14(1-2):426–33. Epub 2009/02/03. https://doi.org/10.1111/j.1582-4934.2008.00650.x.

    Article  CAS  PubMed  Google Scholar 

  57. Ihara F, Sakurai D, Horinaka A, Makita Y, Fujikawa A, Sakurai T, et al. CD45RA-Foxp3high regulatory T-cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma. Cancer Immunol Immunother. 2017; https://doi.org/10.1007/s00262-017-2021-z.

  58. Alhamarneh O, Amarnath SM, Stafford ND, Greenman J. Regulatory T-cells: what role do they play in antitumor immunity in patients with head and neck cancer? Head Neck. 2008;30(2):251–61. Epub 2008/01/04. https://doi.org/10.1002/hed.20739.

    Article  PubMed  Google Scholar 

  59. Jones E, Dahm-Vicker M, Simon AK, Green A, Powrie F, Cerundolo V, et al. Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice. Cancer Immun. 2002;2:1. Epub 2003/05/16

    PubMed  Google Scholar 

  60. Knutson KL, Dang Y, Lu H, Lukas J, Almand B, Gad E, et al. IL-2 immunotoxin therapy modulates tumor-associated regulatory T-cells and leads to lasting immune-mediated rejection of breast cancers in neu-transgenic mice. J Immunol. 2006;177(1):84–91. Epub 2006/06/21

    Article  CAS  PubMed  Google Scholar 

  61. Golgher D, Jones E, Powrie F, Elliott T, Gallimore A. Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens. Eur J Immunol. 2002;32(11):3267–75. Epub 2003/01/31. https://doi.org/10.1002/1521-4141(200211)32:11<3267::AID-IMMU3267>3.0.CO;2-1.

    Article  CAS  PubMed  Google Scholar 

  62. Ge Y, Domschke C, Stoiber N, Schott S, Heil J, Rom J, et al. Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome. Cancer Immunol Immunother. 2012;61(3):353–62. Epub 2011/09/15. https://doi.org/10.1007/s00262-011-1106-3.

    Article  CAS  PubMed  Google Scholar 

  63. Gritzapis AD, Voutsas IF, Baxevanis CN. Ontak reduces the immunosuppressive tumor environment and enhances successful therapeutic vaccination in HER-2/neu-tolerant mice. Cancer Immunol Immunother. 2012;61(3):397–407. Epub 2011/09/20. https://doi.org/10.1007/s00262-011-1113-4.

    Article  CAS  PubMed  Google Scholar 

  64. Litzinger MT, Fernando R, Curiel TJ, Grosenbach DW, Schlom J, Palena C. IL-2 immunotoxin denileukin diftitox reduces regulatory T-cells and enhances vaccine-mediated T-cell immunity. Blood. 2007;110(9):3192–201. https://doi.org/10.1182/blood-2007-06-094615. Epub 2007/07/10. PubMed PMID: 17616639; PubMed Central PMCID: PMC2200901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Sutmuller RP, van Duivenvoorde LM, van Elsas A, Schumacher TN, Wildenberg ME, Allison JP, et al. Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T-cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J Exp Med. 2001;194(6):823–32. Epub 2001/09/19. PubMed PMID: 11560997; PubMed Central PMCID: PMC2195955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Ferris RL, Whiteside TL, Ferrone S. Immune escape associated with functional defects in antigen-processing machinery in head and neck cancer. Clin Cancer Res. 2006;12(13):3890–5. Epub 2006/07/05. https://doi.org/10.1158/1078-0432.CCR-05-2750.

    Article  CAS  PubMed  Google Scholar 

  67. Wang S, Chen L. T lymphocyte co-signaling pathways of the B7-CD28 family. Cell Mol Immunol. 2004;1(1):37–42. Epub 2005/10/11

    PubMed  Google Scholar 

  68. Marincola FM, Jaffee EM, Hicklin DJ, Ferrone S. Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv Immunol. 2000;74:181–273. Epub 1999/12/22

    Article  CAS  PubMed  Google Scholar 

  69. Vambutas A, DeVoti J, Pinn W, Steinberg BM, Bonagura VR. Interaction of human papillomavirus type 11 E7 protein with TAP-1 results in the reduction of ATP-dependent peptide transport. Clin Immunol. 2001;101(1):94–9. Epub 2001/10/03. https://doi.org/10.1006/clim.2001.5094.

    Article  CAS  PubMed  Google Scholar 

  70. Bergmann C, Strauss L, Wieckowski E, Czystowska M, Albers A, Wang Y, et al. Tumor-derived microvesicles in sera of patients with head and neck cancer and their role in tumor progression. Head Neck. 2009;31(3):371–80. https://doi.org/10.1002/hed.20968. Epub 2008/12/17. PubMed PMID: 19073006; PubMed Central PMCID: PMC2647573

    Article  PubMed  PubMed Central  Google Scholar 

  71. Thery C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9(8):581–93. Epub 2009/06/06. https://doi.org/10.1038/nri2567.

    Article  CAS  PubMed  Google Scholar 

  72. Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med. 2001;7(3):297–303. Epub 2001/03/07. https://doi.org/10.1038/85438.

    Article  CAS  PubMed  Google Scholar 

  73. Zeelenberg IS, Ostrowski M, Krumeich S, Bobrie A, Jancic C, Boissonnas A, et al. Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses. Cancer Res. 2008;68(4):1228–35. Epub 2008/02/19. https://doi.org/10.1158/0008-5472.CAN-07-3163.

    Article  CAS  PubMed  Google Scholar 

  74. Zeelenberg IS, van Maren WW, Boissonnas A, Van Hout-Kuijer MA, Den Brok MH, Wagenaars JA, et al. Antigen localization controls T-cell-mediated tumor immunity. J Immunol. 2011;187(3):1281–8. Epub 2011/06/28. https://doi.org/10.4049/jimmunol.1003905.

    Article  CAS  PubMed  Google Scholar 

  75. Kim JW, Wieckowski E, Taylor DD, Reichert TE, Watkins S, Whiteside TL. Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin Cancer Res. 2005;11(3):1010–20. Epub 2005/02/15

    CAS  PubMed  Google Scholar 

  76. Clayton A, Mitchell JP, Court J, Linnane S, Mason MD, Tabi Z. Human tumor-derived exosomes down-modulate NKG2D expression. J Immunol. 2008;180(11):7249–58. Epub 2008/05/21

    Article  CAS  PubMed  Google Scholar 

  77. Whiteside TL. Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour-derived exosomes). Biochem Soc Trans. 2013;41(1):245–51. Epub 2013/01/30. https://doi.org/10.1042/BST20120265.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Ludwig S, Floros T, Theodoraki MN, Hong CS, Jackson EK, Lang S, et al. Suppression of lymphocyte functions by plasma exosomes correlates with disease activity in patients with head and neck cancer. Clin Cancer Res. 2017; https://doi.org/10.1158/1078-0432.CCR-16-2819.

  79. Whiteside TL, Demaria S, Rodriguez-Ruiz ME, Zarour HM, Melero I. Emerging opportunities and challenges in cancer immunotherapy. Clin Cancer Res. 2016;22(8):1845–55. https://doi.org/10.1158/1078-0432.CCR-16-0049. Epub 2016/04/17. PubMed PMID: 27084738; PubMed Central PMCID: PMC4943317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Ludwig S, Floros T, Theodoraki MN, Hong CS, Jackson EK, Lang S, et al. Suppression of lymphocyte functions by plasma exosomes correlates with disease activity in patients with head and neck cancer. Clin Cancer Res. 2017;23(16):4843–54. https://doi.org/10.1158/1078-0432.CCR-16-2819. PubMed PMID: 28400428; PubMed Central PMCID: PMCPMC5559308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Alegre E, Rebmann V, Lemaoult J, Rodriguez C, Horn PA, Diaz-Lagares A, et al. In vivo identification of an HLA-G complex as ubiquitinated protein circulating in exosomes. Eur J Immunol. 2013;43(7):1933–9. Epub 2013/04/17. https://doi.org/10.1002/eji.201343318.

    Article  CAS  PubMed  Google Scholar 

  82. Grange C, Tapparo M, Tritta S, Deregibus MC, Battaglia A, Gontero P, et al. Role of HLA-G and extracellular vesicles in renal cancer stem cell-induced inhibition of dendritic cell differentiation. BMC Cancer. 2015;15:1009. https://doi.org/10.1186/s12885-015-2025-z. Epub 2015/12/26. PubMed PMID: 26704308; PubMed Central PMCID: PMC4690241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Konig L, Kasimir-Bauer S, Hoffmann O, Bittner AK, Wagner B, Manvailer LF, et al. The prognostic impact of soluble and vesicular HLA-G and its relationship to circulating tumor cells in neoadjuvant treated breast cancer patients. Human Immunol. 2016. Epub 2016/01/23; https://doi.org/10.1016/j.humimm.2016.01.002.

  84. Valenti R, Huber V, Iero M, Filipazzi P, Parmiani G, Rivoltini L. Tumor-released microvesicles as vehicles of immunosuppression. Cancer Res. 2007;67(7):2912–5. Epub 2007/04/06. https://doi.org/10.1158/0008-5472.CAN-07-0520.

    Article  CAS  PubMed  Google Scholar 

  85. Valenti R, Huber V, Filipazzi P, Pilla L, Sovena G, Villa A, et al. Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on T lymphocytes. Cancer Res. 2006;66(18):9290–8. Epub 2006/09/20. https://doi.org/10.1158/0008-5472.CAN-06-1819.

    Article  CAS  PubMed  Google Scholar 

  86. Taylor DD, Gercel-Taylor C. Tumour-derived exosomes and their role in cancer-associated T-cell signalling defects. Br J Cancer. 2005;92(2):305–11. https://doi.org/10.1038/sj.bjc.6602316. Epub 2005/01/19. PubMed PMID: 15655551; PubMed Central PMCID: PMC2361848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Szajnik M, Czystowska M, Szczepanski MJ, Mandapathil M, Whiteside TL. Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T-cells (Treg). PLoS One. 2010;5(7):e11469. https://doi.org/10.1371/journal.pone.0011469. Epub 2010/07/28. PubMed PMID: 20661468; PubMed Central PMCID: PMC2908536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wieckowski EU, Visus C, Szajnik M, Szczepanski MJ, Storkus WJ, Whiteside TL. Tumor-derived microvesicles promote regulatory T-cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes. J Immunol. 2009;183(6):3720–30. https://doi.org/10.4049/jimmunol.0900970. Epub 2009/08/21. PubMed PMID: 19692638; PubMed Central PMCID: PMC3721354

    Article  CAS  PubMed  Google Scholar 

  89. Albers AE, Kaufmann AM. Therapeutic human papillomavirus vaccination. Public Health Genomics. 2009;12(5–6):331–42. Epub 2009/08/18. https://doi.org/10.1159/000214923.

    Article  PubMed  Google Scholar 

  90. Hoffmann TK, Arsov C, Schirlau K, Bas M, Friebe-Hoffmann U, Klussmann JP, et al. T-cells specific for HPV16 E7 epitopes in patients with squamous cell carcinoma of the oropharynx. Int J Cancer. 2006;118(8):1984–91. Epub 2005/11/15. https://doi.org/10.1002/ijc.21565.

    Article  CAS  PubMed  Google Scholar 

  91. Ritz U, Momburg F, Pilch H, Huber C, Maeurer MJ, Seliger B. Deficient expression of components of the MHC class I antigen processing machinery in human cervical carcinoma. Int J Oncol. 2001;19(6):1211–20. Epub 2001/11/20

    CAS  PubMed  Google Scholar 

  92. DeLeo AB, Whiteside TL. Development of multi-epitope vaccines targeting wild-type sequence p53 peptides. Expert Rev Vaccines. 2008;7(7):1031–40. Epub 2008/09/05. https://doi.org/10.1586/14760584.7.7.1031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Sakakura K, Chikamatsu K, Furuya N, Appella E, Whiteside TL, Deleo AB. Toward the development of multi-epitope p53 cancer vaccines: an in vitro assessment of CD8(+) T-cell responses to HLA class I-restricted wild-type sequence p53 peptides. Clin Immunol. 2007;125(1):43–51. https://doi.org/10.1016/j.clim.2007.05.015. Epub 2007/07/17. PubMed PMID: 17631051; PubMed Central PMCID: PMC2583371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Baskic D, Vujanovic L, Arsenijevic N, Whiteside TL, Myers EN, Vujanovic NL. Suppression of natural killer-cell and dendritic-cell apoptotic tumoricidal activity in patients with head and neck cancer. Head Neck. 2013;35(3):388–98. Epub 2012/04/11. https://doi.org/10.1002/hed.22968.

    Article  PubMed  Google Scholar 

  95. Seliger B, Maeurer MJ, Ferrone S. Antigen-processing machinery breakdown and tumor growth. Immunol Today. 2000;21(9):455–64. Epub 2000/08/23

    Article  CAS  PubMed  Google Scholar 

  96. Sistigu A, Viaud S, Chaput N, Bracci L, Proietti E, Zitvogel L. Immunomodulatory effects of cyclophosphamide and implementations for vaccine design. Semin Immunopathol. 2011;33(4):369–83. Epub 2011/05/26. https://doi.org/10.1007/s00281-011-0245-0.

    Article  CAS  PubMed  Google Scholar 

  97. Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother. 2009;58(1):49–59. https://doi.org/10.1007/s00262-008-0523-4. Epub 2008/05/01. PubMed PMID: 18446337; PubMed Central PMCID: PMC3401888

    Article  CAS  PubMed  Google Scholar 

  98. Chikamatsu K, Sakakura K, Toyoda M, Takahashi K, Yamamoto T, Masuyama K. Immunosuppressive activity of CD14+ HLA-DR- cells in squamous cell carcinoma of the head and neck. Cancer Sci. 2012;103(6):976–83. Epub 2012/03/01. https://doi.org/10.1111/j.1349-7006.2012.02248.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Vincent J, Mignot G, Chalmin F, Ladoire S, Bruchard M, Chevriaux A, et al. 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T-cell-dependent antitumor immunity. Cancer Res. 2010;70(8):3052–61. Epub 2010/04/15. https://doi.org/10.1158/0008-5472.CAN-09-3690.

    Article  CAS  PubMed  Google Scholar 

  100. Bergmann C, Strauss L, Wang Y, Szczepanski MJ, Lang S, Johnson JT, et al. T regulatory type 1 cells in squamous cell carcinoma of the head and neck: mechanisms of suppression and expansion in advanced disease. Clin Cancer Res. 2008;14(12):3706–15. https://doi.org/10.1158/1078-0432.CCR-07-5126. Epub 2008/06/19. PubMed PMID: 18559587; PubMed Central PMCID: PMC3708468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Jie HB, Schuler PJ, Lee SC, Srivastava RM, Argiris A, Ferrone S, et al. CTLA-4(+) Regulatory T-cells increased in cetuximab-treated head and neck cancer patients suppress NK cell cytotoxicity and correlate with poor prognosis. Cancer Res. 2015;75(11):2200–10. https://doi.org/10.1158/0008-5472.CAN-14-2788. PubMed PMID: 25832655; PubMed Central PMCID: PMCPMC4452385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Chen C, Wei Y, Hummel M, Hoffmann TK, Gross M, Kaufmann AM, et al. Evidence for epithelial-mesenchymal transition in cancer stem cells of head and neck squamous cell carcinoma. PLoS One. 2011;6(1):e16466. Epub 2011/02/10. PubMed PMID: 21304586; PubMed Central PMCID: PMCPMC3029362. https://doi.org/10.1371/journal.pone.0016466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Sun Z, Hu W, Xu J, Kaufmann AM, Albers AE. MicroRNA-34a regulates epithelial-mesenchymal transition and cancer stem cell phenotype of head and neck squamous cell carcinoma in vitro. Int J Oncol. 2015;47(4):1339–50. https://doi.org/10.3892/ijo.2015.3142.

    Article  CAS  PubMed  Google Scholar 

  104. Qian X, Wagner S, Ma C, Coordes A, Gekeler J, Klussmann JP, et al. Prognostic significance of ALDH1A1-positive cancer stem cells in patients with locally advanced, metastasized head and neck squamous cell carcinoma. J Cancer Res Clin Oncol. 2014;140(7):1151–8. Epub 2014/04/29. https://doi.org/10.1007/s00432-014-1685-4.

    Article  CAS  PubMed  Google Scholar 

  105. Qian X, Wagner S, Ma C, Klussmann JP, Hummel M, Kaufmann AM, et al. ALDH1-positive cancer stem-like cells are enriched in nodal metastases of oropharyngeal squamous cell carcinoma independent of HPV status. Oncol Rep. 2013;29(5):1777–84. Epub 2013/03/14. https://doi.org/10.3892/or.2013.2340.

    Article  CAS  PubMed  Google Scholar 

  106. Chen YC, Chang CJ, Hsu HS, Chen YW, Tai LK, Tseng LM, et al. Inhibition of tumorigenicity and enhancement of radiochemosensitivity in head and neck squamous cell cancer-derived ALDH1-positive cells by knockdown of Bmi-1. Oral Oncol. 2010;46(3):158–65. Epub 2009/12/29. https://doi.org/10.1016/j.oraloncology.2009.11.007.

    Article  CAS  PubMed  Google Scholar 

  107. Chen YC, Chen YW, Hsu HS, Tseng LM, Huang PI, Lu KH, et al. Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer. Biochem Biophys Res Commun. 2009;385(3):307–13. Epub 2009/05/20. https://doi.org/10.1016/j.bbrc.2009.05.048.

    Article  CAS  PubMed  Google Scholar 

  108. Visus C, Ito D, Amoscato A, Maciejewska-Franczak M, Abdelsalem A, Dhir R, et al. Identification of human aldehyde dehydrogenase 1 family member A1 as a novel CD8+ T-cell-defined tumor antigen in squamous cell carcinoma of the head and neck. Cancer Res. 2007;67(21):10538–45. Epub 2007/11/03. https://doi.org/10.1158/0008-5472.CAN-07-1346.

    Article  CAS  PubMed  Google Scholar 

  109. Kiessling A, Schmitz M, Stevanovic S, Weigle B, Holig K, Fussel M, et al. Prostate stem cell antigen: identification of immunogenic peptides and assessment of reactive CD8+ T-cells in prostate cancer patients. Int J Cancer J Int Cancer. 2002;102(4):390–7. https://doi.org/10.1002/ijc.10713.

    Article  CAS  Google Scholar 

  110. Xu Q, Liu G, Yuan X, Xu M, Wang H, Ji J, et al. Antigen-specific T-cell response from dendritic cell vaccination using cancer stem-like cell-associated antigens. Stem Cells. 2009;27(8):1734–40. Epub 2009/06/19. https://doi.org/10.1002/stem.102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Garcia-Hernandez Mde L, Gray A, Hubby B, Klinger OJ, Kast WM. Prostate stem cell antigen vaccination induces a long-term protective immune response against prostate cancer in the absence of autoimmunity. Cancer Res. 2008;68(3):861–9. Epub 2008/02/05. https://doi.org/10.1158/0008-5472.CAN-07-0445.

    Article  CAS  PubMed  Google Scholar 

  112. Pellegatta S, Poliani PL, Corno D, Menghi F, Ghielmetti F, Suarez-Merino B, et al. Neurospheres enriched in cancer stem-like cells are highly effective in eliciting a dendritic cell-mediated immune response against malignant gliomas. Cancer Res. 2006;66(21):10247–52. Epub 2006/11/03. https://doi.org/10.1158/0008-5472.CAN-06-2048.

    Article  CAS  PubMed  Google Scholar 

  113. Dhodapkar MV. Immunity to stemness genes in human cancer. Curr Opin Immunol. 2010;22(2):245–50. https://doi.org/10.1016/j.coi.2010.01.011. Epub 2010/02/11. PubMed PMID: 20144857; PubMed Central PMCID: PMC2892711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Liao T, Kaufmann AM, Qian X, Sangvatanakul V, Chen C, Kube T, et al. Susceptibility to cytotoxic T-cell lysis of cancer stem cells derived from cervical and head and neck tumor cell lines. J Cancer Res Clin Oncol. 2013;139(1):159–70. Epub 2012/09/25. https://doi.org/10.1007/s00432-012-1311-2.

    Article  CAS  PubMed  Google Scholar 

  115. Visus C, Wang Y, Lozano-Leon A, Ferris RL, Silver S, Szczepanski MJ, et al. Targeting ALDH(bright) human carcinoma-initiating cells with ALDH1A1-specific CD8(+) T-cells. Clin Cancer Res. 2011;17(19):6174–84. https://doi.org/10.1158/1078-0432.CCR-11-1111. Epub 2011/08/23. PubMed PMID: 21856769; PubMed Central PMCID: PMCPMC3186874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Ning N, Pan Q, Zheng F, Teitz-Tennenbaum S, Egenti M, Yet J, et al. Cancer stem cell vaccination confers significant antitumor immunity. Cancer Res. 2012;72(7):1853–64. https://doi.org/10.1158/0008-5472.CAN-11-1400. PubMed PMID: 22473314; PubMed Central PMCID: PMCPMC3320735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Hu Y, Lu L, Xia Y, Chen X, Chang AE, Hollingsworth RE, et al. Therapeutic efficacy of cancer stem cell vaccines in the adjuvant setting. Cancer Res. 2016;76(16):4661–72. https://doi.org/10.1158/0008-5472.CAN-15-2664. PubMed PMID: 27325649; PubMed Central PMCID: PMCPMC4987233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Hildesheim A, Herrero R, Wacholder S, Rodriguez AC, Solomon D, Bratti MC, et al. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among young women with preexisting infection: a randomized trial. JAMA. 2007;298(7):743–53. Epub 2007/08/21. https://doi.org/10.1001/jama.298.7.743.

    Article  CAS  PubMed  Google Scholar 

  119. Zandberg DP, Rollins S, Goloubeva O, Morales RE, Tan M, Taylor R, et al. A phase I dose escalation trial of MAGE-A3- and HPV16-specific peptide immunomodulatory vaccines in patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN). Cancer Immunol Immunother. 2015;64(3):367–79. https://doi.org/10.1007/s00262-014-1640-x. PubMed PMID: 25537079; PubMed Central PMCID: PMCPMC4381442

    Article  CAS  PubMed  Google Scholar 

  120. Nikitina EY, Clark JI, Van Beynen J, Chada S, Virmani AK, Carbone DP, et al. Dendritic cells transduced with full-length wild-type p53 generate antitumor cytotoxic T lymphocytes from peripheral blood of cancer patients. Clin Cancer Res. 2001;7(1):127–35. Epub 2001/02/24

    CAS  PubMed  Google Scholar 

  121. Azuma K, Shichijo S, Maeda Y, Nakatsura T, Nonaka Y, Fujii T, et al. Mutated p53 gene encodes a nonmutated epitope recognized by HLA-B*4601-restricted and tumor cell-reactive CTLs at tumor site. Cancer Res. 2003;63(4):854–8. Epub 2003/02/20

    CAS  PubMed  Google Scholar 

  122. Schuler PJ, Harasymczuk M, Visus C, Deleo A, Trivedi S, Lei Y, et al. Phase I dendritic cell p53 peptide vaccine for head and neck cancer. Clin Cancer Res. 2014;20(9):2433–44. https://doi.org/10.1158/1078-0432.CCR-13-2617. PubMed PMID: 24583792; PubMed Central PMCID: PMCPMC4017234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Swanson MS, Sinha UK. Rationale for combined blockade of PD-1 and CTLA-4 in advanced head and neck squamous cell cancer-review of current data. Oral Oncol. 2015;51(1):12–5. https://doi.org/10.1016/j.oraloncology.2014.10.010.

    Article  CAS  PubMed  Google Scholar 

  124. Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–67. https://doi.org/10.1056/NEJMoa1602252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Harrington KJ, Ferris RL, Blumenschein G Jr, Colevas AD, Fayette J, Licitra L, et al. Nivolumab versus standard, single-agent therapy of investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol. 2017; https://doi.org/10.1016/S1470-2045(17)30421-7.

  126. Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016;17(7):956–65. https://doi.org/10.1016/S1470-2045(16)30066-3.

    Article  CAS  PubMed  Google Scholar 

  127. Chow LQ, Haddad R, Gupta S, Mahipal A, Mehra R, Tahara M, et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results from the phase Ib KEYNOTE-012 Expansion Cohort. J Clin Oncol. 2016; https://doi.org/10.1200/JCO.2016.68.1478.

  128. Li J, Shayan G, Avery L, Jie HB, Gildener-Leapman N, Schmitt N, et al. Tumor-infiltrating Tim-3+ T-cells proliferate avidly except when PD-1 is co-expressed: evidence for intracellular cross talk. Oncoimmunology. 2016;5(10):e1200778. https://doi.org/10.1080/2162402X.2016.1200778. PubMed PMID: 27853635; PubMed Central PMCID: PMCPMC5087305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Shayan G, Srivastava R, Li J, Schmitt N, Kane LP, Ferris RL. Adaptive resistance to anti-PD1 therapy by Tim-3 upregulation is mediated by the PI3K-Akt pathway in head and neck cancer. Oncoimmunology. 2017;6(1):e1261779. https://doi.org/10.1080/2162402X.2016.1261779. PubMed PMID: 28197389; PubMed Central PMCID: PMCPMC5283618

    Article  CAS  PubMed  Google Scholar 

  130. van Herpen CM, van der Voort R, van der Laak JA, Klasen IS, de Graaf AO, van Kempen LC, et al. Intratumoral rhIL-12 administration in head and neck squamous cell carcinoma patients induces B cell activation. Int J Cancer J Int Cancer. 2008;123(10):2354–61. https://doi.org/10.1002/ijc.23756.

    Article  CAS  Google Scholar 

  131. De Stefani A, Forni G, Ragona R, Cavallo G, Bussi M, Usai A, et al. Improved survival with perilymphatic interleukin 2 in patients with resectable squamous cell carcinoma of the oral cavity and oropharynx. Cancer. 2002;95(1):90–7. https://doi.org/10.1002/cncr.10654.

    Article  PubMed  Google Scholar 

  132. Freeman SM, Franco JL, Kenady DE, Baltzer L, Roth Z, Brandwein HJ, et al. A phase 1 safety study of an IRX-2 regimen in patients with squamous cell carcinoma of the head and neck. Am J Clin Oncol. 2011;34(2):173–8. https://doi.org/10.1097/COC.0b013e3181dbb9d8.

    Article  CAS  PubMed  Google Scholar 

  133. Karcher J, Dyckhoff G, Beckhove P, Reisser C, Brysch M, Ziouta Y, et al. Antitumor vaccination in patients with head and neck squamous cell carcinomas with autologous virus-modified tumor cells. Cancer Res. 2004;64(21):8057–61. https://doi.org/10.1158/0008-5472.CAN-04-1545.

    Article  CAS  PubMed  Google Scholar 

  134. Victora GD, Socorro-Silva A, Volsi EC, Abdallah K, Lima FD, Smith RB, et al. Immune response to vaccination with DNA-Hsp65 in a phase I clinical trial with head and neck cancer patients. Cancer Gene Ther. 2009;16(7):598–608. https://doi.org/10.1038/cgt.2009.9.

    Article  CAS  PubMed  Google Scholar 

  135. Smith C, Tsang J, Beagley L, Chua D, Lee V, Li V, et al. Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy. Cancer Res. 2012;72(5):1116–25. https://doi.org/10.1158/0008-5472.CAN-11-3399.

    Article  CAS  PubMed  Google Scholar 

  136. Molling JW, Moreno M, de Groot J, van der Vliet HJ, von Blomberg BM, van den Eertwegh AJ, et al. Chronically stimulated mouse invariant NKT-cell lines have a preserved capacity to enhance protection against experimental tumor metastases. Immunol Lett. 2008;118(1):36–43. https://doi.org/10.1016/j.imlet.2008.02.007.

    Article  CAS  PubMed  Google Scholar 

  137. Shibuya TY, Wei WZ, Zormeier M, Ensley J, Sakr W, Mathog RH, et al. Anti-CD3/anti-CD28 bead stimulation overcomes CD3 unresponsiveness in patients with head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2000;126(4):473–9.

    Article  CAS  PubMed  Google Scholar 

  138. Yoshitake Y, Fukuma D, Yuno A, Hirayama M, Nakayama H, Tanaka T, et al. Phase II clinical trial of multiple peptide vaccination for advanced head and neck cancer patients revealed induction of immune responses and improved OS. Clin Cancer Res. 2015;21(2):312–21. https://doi.org/10.1158/1078-0432.CCR-14-0202.

    Article  CAS  PubMed  Google Scholar 

  139. Seixas-Silva JA Jr, Richards T, Khuri FR, Wieand HS, Kim E, Murphy B, et al. Phase 2 bioadjuvant study of interferon alfa-2a, isotretinoin, and vitamin E in locally advanced squamous cell carcinoma of the head and neck: long-term follow-up. Arch Otolaryngol Head Neck Surg. 2005;131(4):304–7. https://doi.org/10.1001/archotol.131.4.304.

    Article  PubMed  Google Scholar 

  140. To WC, Wood BG, Krauss JC, Strome M, Esclamado RM, Lavertu P, et al. Systemic adoptive T-cell immunotherapy in recurrent and metastatic carcinoma of the head and neck: a phase 1 study. Arch Otolaryngol Head Neck Surg. 2000;126(10):1225–31.

    Article  CAS  PubMed  Google Scholar 

  141. Kurosaki M, Horiguchi S, Yamasaki K, Uchida Y, Motohashi S, Nakayama T, et al. Migration and immunological reaction after the administration of alphaGalCer-pulsed antigen-presenting cells into the submucosa of patients with head and neck cancer. Cancer Immunol Immunother: CII. 2011;60(2):207–15. https://doi.org/10.1007/s00262-010-0932-z.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China

    Xu Qian

  2. Department of Clinical Laboratory, Zhejiang Cancer Hospital, Hangzhou, China

    Xu Qian

  3. Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China

    Xu Qian

  4. Department of Otorhinolaryngology, Head and Neck Surgery, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany

    Xu Qian & Andreas E. Albers

  5. Department of Otolaryngology, Head and Neck Surgery, University of Ulm, Ulm, Germany

    Thomas K. Hoffmann

  6. Clinic for Gynecology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany

    Andreas M. Kaufmann

  7. Berlin Institute of Health, Berlin, Germany

    Andreas M. Kaufmann & Andreas E. Albers

Authors
  1. Xu Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas K. Hoffmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andreas M. Kaufmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andreas E. Albers
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andreas E. Albers .

Editor information

Editors and Affiliations

  1. Research Center for Immunodeficiencies Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Qian, X., Hoffmann, T.K., Kaufmann, A.M., Albers, A.E. (2020). Immunopathology as a Basis for Immunotherapy of Head and Neck Squamous Cell Carcinoma. In: Rezaei, N. (eds) Cancer Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-57949-4_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-57949-4_13

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-57948-7

  • Online ISBN: 978-3-030-57949-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation