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Immune System in Patients with Head and Neck Carcinoma


Authors: S. Partlová 1,2;  J. Bouček 3;  K. Kloudová 1,2;  M. Zábrodský 3;  R. Špíšek 1,2;  A. Fialová 2
Authors‘ workplace: Sotio a.  s., Praha 1;  Ústav imunologie, 2. LF UK a FN v Motole, Praha 2;  Klinika otorinolaryngologie a chirurgie hlavy a krku 1. LF UK a FN v Motole, Praha 3
Published in: Klin Onkol 2015; 28(Supplementum 4): 86-94
Category: Specials
doi: https://doi.org/10.14735/amko20154S86

Overview

The insight into the biological nature of head and neck squamous cell carcinoma has evolved significantly in the last few years. Tobacco use and alcohol consumption are proven risk factors of head and neck squamous cell carcinoma. Cancer patients possessing such a tumor are generally elderly, mostly in fifth or sixth decade of life. In addition, significant association of head and neck squamous cell carcinoma with infection by human papillomavirus (HPV) was proven. HPV is now considered to be one of the most important risk factors, particularly for oropharyngeal carcinoma. HPV‑ positive tumors of oropharynx are associated with significantly better prognosis. Experimental and clinical data indicate that HPV‑ positive and HPV‑ negative tumors can be considered as two different entities and it has not been clarified which factors are crucial for better prognosis of HPV‑ positive tumors. The character of immune reaction, which contributes to distinct prognosis, may be one of the important factors. This review summarizes current knowledge concerning various aspects of anti‑tumor immune responses in HPV‑ positive and HPV‑ negative tumors. Recent studies have shown that a broad repertoire of tumor‑ infiltrating HPV‑ specific T-cells is detectable in almost all patients with HPV‑ positive tumors. Despite this, there is a development of tumor, which may be facilitated by abnormalities in antigen processing, T-cell dysfunction or prevalence of immunosuppressive cells. Nonetheless, the immunologic profile of HPV‑ positive vs. HPV‑ negative head and neck squamous cell carcinoma is associated with better outcome, and HPV‑ specific immune response is suggested to play an essential role in the better response to conventional therapy of HPV‑ positive patients. We also discuss HPV‑ specific antitumor immunotherapy approaches, which are now tested in clinical trials.

Key words:
head and neck cancer –  human papillomavirus –  immune system –  T-lymphocytes –  immunotherapy

This study was supported by grant Internal Grant Agency of the Czech Ministry of Health No. NT 11542, FH Motol – grant No. 00064203 and by grants SVV 266513, UNCE 204013 and PRVOUK 27-1.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
31. 7. 2015

Accepted:
22. 8. 2015


Sources

1. Guo T, Califano JA. Molecular biology and immunology of head and neck cancer. Surg Oncol Clin N Am 2015; 24(3): 397– 407. doi: 10.1016/ j.soc.2015.03.002.

2. Psyrri A, Burtness B, Harari PM et al. Head and neck cancer. J Oncol 2009; 2009: 358098. doi: 10.1155/ 2009/ 358098.

3. Ferlay J, Shin HR, Bray F et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127(12): 2893– 2917. doi: 10.1002/ ijc.25516.

4. Young D, Xiao CC, Murphy B et al. Increase in head and neck cancer in younger patients due to human papillomavirus (HPV). Oral Oncol 2015; 51(8): 727– 730. doi: 10.1016/ j.oraloncology.2015.03.015.

5. D‘Souza G, Kreimer AR, Viscidi R et al. Case‑ control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 2007; 356(19): 1944– 1956.

6. Tachezy R, Klozar J, Saláková M et al. HPV and other risk factors of oral cavity/ oropharyngeal cancer in the Czech Republic. Oral Dis 2005; 11(3): 181– 185.

7. Marur S, D‘Souza G, Westra WH et al. HPV‑associated head and neck cancer: a virus‑related cancer epidemic. Lancet Oncol 2010; 11(8): 781– 789. doi: 10.1016/ S1470‑ 2045(10)70017‑ 6.

8. Klozar J, Tachezy R. What are the implications of human papillomavirus status in oropharyngeal tumors for clinical practice? Curr Opin Otolaryngol Head Neck Surg 2014; 22(2): 90– 94. doi: 10.1097/ MOO.0000000000000030.

9. Sepiashvili L, Bruce JP, Huang SH et al. Novel insights into head and neck cancer using next‑ generation „omic“ technologies. Cancer Res 2015; 75(3): 480– 486. doi: 10.1158/ 0008‑ 5472.CAN‑ 14‑ 3124.

10. Stransky N, Egloff AM, Tward AD et al. The mutational landscape of head and neck squamous cell carcinoma. Science 2011; 333(6046): 1157– 1160. doi: 10.1126/ science.1208130.

11. Poeta ML, Manola J, Goldwasser MA et al. TP53 mutations and survival in squamous‑ cell carcinoma of the head and neck. N Engl J Med 2007; 357(25): 2552– 2561.

12. Skinner HD, Sandulache VC, Ow TJ et al. TP53 disruptive mutations lead to head and neck cancer treatment failure through inhibition of radiation‑induced senescence. Clin Cancer Res 2012; 18(1): 290– 300. doi: 10.1158/ 1078‑ 0432.CCR‑ 11‑ 2260.

13. Cancer Genome Atlas Network. Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 2015; 517(7536): 576– 582. doi: 10.1038/ nature14129.

14. Mrhalova M, Plzak J, Betka J et al. Epidermal growth factor receptor –  its expression and copy numbers of EGFR gene in patients with head and neck squamous cell carcinomas. Neoplasma 2005; 52(4): 338– 343.

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

16. Albers A, Abe K, Hunt J 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– 11155.

17. Spanos WC, Nowicki P, Lee DW et al. Immune response during therapy with cisplatin or radiation for human papillomavirus‑related head and neck cancer. Arch Otolaryngol Head Neck Surg 2009; 135(11): 1137– 1146. doi: 10.1001/ archoto.2009.159.

18. Duray A, Demoulin S, Hubert P et al. Immune suppression in head and neck cancers: a review. Clin Dev Immunol 2010; 2010: 701657. doi: 10.1155/ 2010/ 701657.

19. Allen CT, Judd NP, Bui JD et al. The clinical implications of antitumor immunity in head and neck cancer. Laryngoscope 2012; 122(1): 144– 157. doi: 10.1002/ lary.21913.

20. Russell S, Angell T, Lechner M et al. Immune cell infiltration patterns and survival in head and neck squamous cell carcinoma. Head Neck Oncol 2013; 5(3): 24.

21. Fridman WH, Pagès F, Sautès‑ Fridman C et al. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 2012; 12(4): 298– 306. doi: 10.1038/ nrc3245.

22. Reichert TE, Day R, Wagner EM et al. 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– 5347.

23. Kuss I, Saito T, Johnson JT et al. Clinical significance of decreased zeta chain expression in peripheral blood lymphocytes of patients with head and neck cancer. Clin Cancer Res 1999; 5(2): 329– 334.

24. Hoffmann TK, Dworacki G, Tsukihiro T 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– 2562.

25. Badoual C, Hans S, Rodriguez J et al. Prognostic value of tumor‑ infiltrating CD4+ T‑ cell subpopulations in head and neck cancers. Clin Cancer Res 2006; 12(2): 465– 472.

26. Zhang YL, Li J, Mo HY et al. Different subsets of tumor infiltrating lymphocytes correlate with NPC progression in different ways. Mol Cancer 2010; 9: 4. doi: 10.1186/ 1476‑ 4598‑ 9‑ 4.

27. Strauss L, Bergmann C, Szczepanski M et al. 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– 4354.

28. Kesselring R, Thiel A, Pries R et al. Human Th17 cells can be induced through head and neck cancer and have a functional impact on HNSCC development. Br J Cancer 2010; 103(8): 1245– 1254. doi: 10.1038/ sj.bjc.6605891.

29. Kanodia S, Fahey LM, Kast WM. Mechanisms used by human papillomaviruses to escape the host immune response. Curr Cancer Drug Targets 2007; 7(1): 79– 89.

30. Iijima N, Goodwin EC, Dimaio D et al. High‑risk human papillomavirus E6 inhibits monocyte differentiation to Langerhans cells. Virology 2013; 444(1– 2): 257– 262. doi: 10.1016/ j.virol.2013.06.020.

31. Kimple RJ, Harari PM, Torres AD et al. Development and characterization of HPV‑ positive and HPV‑ negative head and neck squamous cell carcinoma tumorgrafts. Clin Cancer Res 2013; 19(4): 855– 864. doi: 10.1158/ 1078‑ 0432.CCR‑ 12‑ 2746.

32. Galon J, Pagès F, Marincola FM et al. Cancer classification using the immunoscore: a worldwide task force. J Transl Med 2012; 10: 205. doi: 10.1186/ 1479‑ 5876‑ 10‑ 205.

33. Leiding JW, Holland SM. Warts and all: human papillomavirus in primary immunodeficiencies. J Allergy Clin Immunol 2012; 130(5): 1030– 1048. doi: 10.1016/ j.jaci.2012.07.049.

34. Kreimer AR, Alberg AJ, Daniel R et al. Oral human papillomavirus infection in adults is associated with sexual behavior and HIV serostatus. J Infect Dis 2004; 189(4): 686– 698.

35. Kim ST, Jeong H, Woo OH et al. Tumor‑ infiltrating lymphocytes, tumor characteristics, and recurrence in patients with early breast cancer. Am J Clin Oncol 2013; 36(3): 224– 231. doi: 10.1097/ COC.0b013e3182467d90.

36. Wansom D, Light E, Worden F 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– 1273. doi: 10.1001/ archoto.2010.211.

37. Turksma AW, Bontkes HJ, van den Heuvel H et al. Effector memory T‑ cell frequencies in relation to tumour stage, location and HPV status in HNSCC patients. Oral Dis 2013; 19(6): 577– 584. doi: 10.1111/ odi.12037.

38. Thurlow JK, Peña Murillo CL, Hunter KD et al. Spectral clustering of microarray data elucidates the roles of microenvironment remodeling and immune responses in survival of head and neck squamous cell carcinoma. J Clin Oncol 2010; 28(17): 2881– 2888. doi: 10.1200/ JCO.2009.24.8724.

39. Nasman A, Romanitan M, Nordfors C et al. Tumor infiltrating CD8+ and Foxp3+ lymphocytes correlate to clinical outcome and human papillomavirus (HPV) status in tonsillar cancer. PLoS One 2012; 7(6): e38711. doi: 10.1371/ journal.pone.0038711.

40. Partlova S, Bouček J, Kloudová K et al. Distinct patterns of intratumoral immune cell infiltrates in patients with HPV‑associated compared to non‑virally induced head and neck squamous cell carcinoma. Oncoimmunology 2015; 4(1): e965570.

41. Badoual C, Hans S, Merillon N et al. PD‑ 1- expressing tumor‑ infiltrating T cells are a favorable prognostic biomarker in HPV‑associated head and neck cancer. Cancer Res 2013; 73(1): 128– 138. doi: 10.1158/ 0008‑ 5472.CAN‑ 12‑ 2606.

42. Sauce D, Almeida JR, Larsen M et al. PD‑ 1 expression on human CD8 T cells depends on both state of differentiation and activation status. AIDS 2007; 21(15): 2005– 2013.

43. Curiel TJ, Coukos G, Zou L et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004; 10(9): 942– 949.

44. Salama P, Phillips M, Grieu F et al. Tumor‑ infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol 2009; 27(2): 186– 192. doi: 10.1200/ JCO.2008.18.7229.

45. Alvaro T, Lejeune M, Salvadó MT et al. Outcome in Hodgkin‘s lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells. Clin Cancer Res 2005; 11(4): 1467– 1473.

46. Piersma SJ, Jordanova ES, van Poelgeest MI et al. High number of intraepithelial CD8+ tumor‑ infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early‑stage cervical cancer. Cancer Res 2007; 67(1): 354– 361.

47. Bron L, Jandus C, Andrejevic‑ Blant S et al. Prognostic value of arginase‑ II expression and regulatory T‑ cell infiltration in head and neck squamous cell carcinoma. Int J Cancer 2013; 132(3): E85– E93. doi: 10.1002/ ijc.27728.

48. Boucek J, Mrkvan T, Chovanec M 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– 433.

49. Heusinkveld M, Goedemans R, Briet RJ et al. Systemic and local human papillomavirus 16- specific T‑ cell immunity in patients with head and neck cancer. Int J Cancer 2012; 131(2): E74– E85. doi: 10.1002/ ijc.26497.

50. Hoffmann TK, Arsov C, Schirlau K 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– 1991.

51. Best SR, Niparko KJ, Pai SI. Biology of human papillomavirus infection and immune therapy for HPV‑related head and neck cancers. Otolaryngol Clin North Am 2012; 45(4): 807– 822. doi: 10.1016/ j.otc.2012.04.005.

52. Kenter GG, Welters MJ, Valentijn AR et al. Vaccination against HPV‑ 16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med 2009; 361(19): doi: 10.1056/ NEJMoa0810097.

53. Comoli P, Pedrazzoli P, Maccario R et al. Cell therapy of stage IV nasopharyngeal carcinoma with autologous Epstein‑Barr virus‑ targeted cytotoxic T lymphocytes. J Clin Oncol 2005; 23(35): 8942– 8949.

54. Chang AE, Li Q, Jiang G et al. Generation of vaccine‑ primed lymphocytes for the treatment of head and neck cancer. Head Neck 2003; 25(3): 198– 209.

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Paediatric clinical oncology Surgery Clinical oncology

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