Characterization of tumor-associated T-lymphocyte subsets and immune checkpoint molecules in head and neck squamous cell carcinoma

Oncotarget

Volumn 8, Issue 27, 2017, Pages 44418-44433

  Lechner, Axel ^a,b   Schlößer, Hans ^a,b   Rothschild, Sacha I ^a,c   Thelen, Martin ^a   Reuter, Sabrina ^a   Zentis, Peter ^d   Shimabukuro Vornhagen, Alexander ^a   Theurich, Sebastian ^a,e   Wennhold, Kerstin ^a   Garcia Marquez, Maria ^a   Tharun, Lars ^b   Quaas, Alexander ^b   Schauss, Astrid ^d   Isensee, Jörg ^a   Hucho, Tim ^a   Huebbers, Christian ^b   von Bergwelt Baildon, Michael ^a   Beutner, Dirk ^b  

^a UNIVERSITY HOSPITAL OF COLOGNE   (Germany)

^b UNIVERSITY OF COLOGNE   (Germany)

^c UNIVERSITY HOSPITAL BASEL   (Switzerland)

^d UNIVERSITY OF COLOGNE   (Germany)

^e MAX PLANCK INSTITUTE FOR NEUROLOGICAL RESEARCH   (Germany)

Author keywords

Head and neck; Immune checkpoint; Microenvironment; Squamous cell carcinoma; T cells

Indexed keywords

CD45RA ANTIGEN; CHEMOKINE RECEPTOR CCR7; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; BIOLOGICAL MARKER; CD274 PROTEIN, HUMAN;

ADULT; AGED; ANTIGEN EXPRESSION; ARTICLE; CANCER STAGING; CD3+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; EARLY CANCER; FEMALE; FLOW CYTOMETRY; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; LYMPHOCYTE COUNT; LYMPHOCYTIC INFILTRATION; MAJOR CLINICAL STUDY; MALE; PERIPHERAL BLOOD MONONUCLEAR CELL; PHENOTYPE; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; TUMOR ASSOCIATED LEUKOCYTE; TUMOR MICROENVIRONMENT; WART VIRUS; CANCER GRADING; GENETICS; HEAD AND NECK TUMOR; IMMUNOLOGY; IMMUNOMODULATION; IMMUNOPHENOTYPING; METABOLISM; MIDDLE AGED; PATHOLOGY; SQUAMOUS CELL CARCINOMA; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; B7-H1 ANTIGEN; BIOMARKERS; CARCINOMA, SQUAMOUS CELL; CTLA-4 ANTIGEN; FEMALE; HEAD AND NECK NEOPLASMS; HUMANS; IMMUNOMODULATION; IMMUNOPHENOTYPING; LYMPHOCYTE COUNT; LYMPHOCYTES, TUMOR-INFILTRATING; MALE; MIDDLE AGED; NEOPLASM GRADING; NEOPLASM STAGING; PHENOTYPE; PROGRAMMED CELL DEATH 1 RECEPTOR; SQUAMOUS CELL CARCINOMA OF HEAD AND NECK; T-LYMPHOCYTE SUBSETS; TUMOR MICROENVIRONMENT;

EID: 85021824297     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.17901     Document Type: Article

References (62)

1. Ramroth H, Dietz A, Becher H. Interaction effects and population-attributable risks for smoking and alcohol on laryngeal cancer and its subsites. A case-control study from Germany. Methods Inf Med. 2004; 43:499-504. doi: 10.1267/METH04050499.
2. Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C, Paleri V, Roberts S. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer systematic review and meta-analysis of trends by time and region. Head Neck. 2013; 35:747-55. doi: 10.1002/hed.22015.
3. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010; 363:24-35. doi: 10.1056/NEJMoa0912217.
4. Albers A, Abe K, Hunt J, Wang J, Lopez-Albaitero A, Schaefer C, Gooding W, Whiteside TL, Ferrone S, DeLeo A, Ferris RL. 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; 65:11146-55. doi: 10.1158/0008-5472.CAN-05-0772.
5. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144:646-74. doi: 10.1016/j.cell.2011.02.013.
6. Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011; 29:235-71. doi: 10.1146/annurevimmunol-031210-101324.
7. Schlößer HA, Drebber U, Kloth M, Thelen M, Rothschild SI, Haase S, Garcia-Marquez M, Wennhold K, Berlth F, Urbanski A, Alakus H, Schauss A, Shimabukuro-Vornhagen A, et al. Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma. Oncoimmunology. 2016; 5: e1100789. doi: 10.1080/2162402X.2015.1100789.
8. Shimabukuro-Vornhagen A, Schlosser HA, Gryschok L, Malcher J, Wennhold K, Garcia-Marquez M, Herbold T, Neuhaus LS, Becker HJ, Fiedler A, Scherwitz P, Koslowsky T, Hake R, et al. Characterization of tumor-associated B-cell subsets in patients with colorectal cancer. Oncotarget. 2014; 5:4651-64. doi: 10.18632/oncotarget.1701.
9. Woo EY, Yeh H, Chu CS, Schlienger K, Carroll RG, Riley JL, Kaiser LR, June CH. Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J Immunol. 2002; 168:4272-6.
10. Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, Rubin SC, Kaiser LR, June CH. Regulatory CD4(+)CD25(+) T cells in tumors from patients with earlystage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res. 2001; 61:4766-72.
11. Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, Drebin JA, Strasberg SM, Eberlein TJ, Goedegebuure PS, Linehan DC. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol. 2002; 169:2756-61.
12. Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeck-Loebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res. 2003; 9:606-12.
13. Whiteside TL. Down-regulation of zeta-chain expression in T cells: a biomarker of prognosis in cancer? Cancer Immunol Immunother. 2004; 53:865-78. doi: 10.1007/s00262-004-0521-0.
14. Wallis SP, Stafford ND, Greenman J. Clinical relevance of immune parameters in the tumor microenvironment of head and neck cancers. Head Neck. 2015; 37:449-59. doi: 10.1002/hed.23736.
15. 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; 13:4345-54. doi: 10.1158/1078-0432.CCR-07-0472.
16. Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay NEH, Mosseri V, Laccourreye O, Bruneval P, Fridman WH, Brasnu DF, Tartour E. Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res. 2006; 12:465-72. doi: 10.1158/1078-0432.CCR-05-1886.
17. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, Tosolini M, Camus M, Berger A, Wind P, Zinzindohoué F, Bruneval P, Cugnenc PH, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006; 313:1960-4. doi: 10.1126/science.1129139.
18. Mlecnik B, Bindea G, Angell HK, Maby P, Angelova M, Tougeron D, Church SE, Lafontaine L, Fischer M, Fredriksen T, Sasso M, Bilocq AM, Kirilovsky A, et al. Integrative Analyses of Colorectal Cancer Show Immunoscore Is a Stronger Predictor of Patient Survival Than Microsatellite Instability. Immunity. 2016; 44:698-711 doi: 10.1016/j.immuni.2016.02.025.
19. Pagès F, Kirilovsky A, Mlecnik B, Asslaber M, Tosolini M, Bindea G, Lagorce C, Wind P, Marliot F, Bruneval P, Zatloukal K, Trajanoski Z, Berger A, et al. In Situ Cytotoxic and Memory T Cells Predict Outcome in Patients With Early-Stage Colorectal Cancer. J Clin Oncol. 2009; 27:5944-51. doi: 10.1200/JCO.2008.19.6147.
20. Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, Lugli A, Zlobec I, Hartmann A, Bifulco C, Nagtegaal ID, Palmqvist R, Masucci GV, et al. Towards the introduction of the "Immunoscore" in the classification of malignant tumours. J Pathol. 2014; 232:199-209. doi: 10.1002/path.4287.
21. Perea F, Bernal M, Sánchez-Palencia A, Carretero J, Torres C, Bayarri C, Gómez-Morales M, Garrido F, Ruiz-Cabello F. The absence of HLA class I expression in nonsmall cell lung cancer correlates with the tumor tissue structure and the pattern of T cell infiltration. Int J Cancer. 2017; 140:888-99. doi: 10.1002/ijc.30489.
22. Näsman A, Andersson E, Nordfors C, Grün N, Johansson H, Munck-Wikland E, Massucci G, Dalianis T, Ramqvist T. MHC class I expression in HPV positive and negative tonsillar squamous cell carcinoma in correlation to clinical outcome. Int J Cancer. 2013; 132:72-81. doi: 10.1002/ijc.27635.
23. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12:252-64. doi: 10.1038/nrc3239.
24. Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. 2008; 224:166-82. doi: 10.1111/j.1600-065X.2008.00662.x.
25. Ferris RL, Blumenschein G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016; 375:1856-67. doi: 10.1056/NEJMoa1602252.
26. Mandapathil M, Lang S, Gorelik E, Whiteside TL. Isolation of functional human regulatory T cells (Treg) from the peripheral blood based on the CD39 expression. J Immunol Methods. 2009; 346:55-63. doi: 10.1016/j.jim.2009.05.004.
27. Yu N, Li X, Song W, Li D, Yu D, Zeng X, Li M, Leng X, Li X. CD4+CD25+CD127low/-T Cells: A More Specific Treg Population in Human Peripheral Blood. Inflammation. 2012; 35:1773-80. doi: 10.1007/s10753-012-9496-8.
28. Beyer M, Classen S, Endl E, Kochanek M, Weihrauch MR, Debey-Pascher S, Knolle PA, Schultze JL, Beyer M, Classen S, Endl E, Kochanek M, Weihrauch MR, et al. Comparative approach to define increased regulatory T cells in different cancer subtypes by combined assessment of CD127 and FOXP3. Clin Dev Immunol. 2011; 2011: 734036. doi: 10.1155/2011/734036.
29. Li H, Ou X, Xiong J, Wang T. HPV16E7 mediates HADC chromatin repression and downregulation of MHC class I genes in HPV16 tumorigenic cells through interaction with an MHC class I promoter. Biochem Biophys Res Commun. 2006; 349:1315-21. doi: 10.1016/j.bbrc.2006.08.182.
30. Pretscher D, Distel LV, Grabenbauer GG, Wittlinger M, Buettner M, Niedobitek G. 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. doi: 10.1186/1471-2407-9-292.
31. Russell S, Angell T, Lechner M, Liebertz D, Correa A, Sinha U, Kokot N, Epstein A. Immune cell infiltration patterns and survival in head and neck squamous cell carcinoma. Head Neck Oncol. 2013; 5: 24.
32. Nguyen N, Bellile E, Thomas D, McHugh J, Rozek L, Virani S, Peterson L, Carey TE, Walline H, Moyer J, Spector M, Perim D, Prince M, et al. Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma. Head Neck. 2016; 38:1074-84. doi: 10.1002/hed.24406.
33. Gooden MJM, de Bock GH, Leffers N, Daemen T, Nijman HW. The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with metaanalysis. Br J Cancer. 2011; 105:93-103. doi: 10.1038/bjc.2011.189.
34. Ogino S, Nosho K, Irahara N, Meyerhardt JA, Baba Y, Shima K, Glickman JN, Ferrone CR, Mino-Kenudson M, Tanaka N, Dranoff G, Giovannucci EL, Fuchs CS. Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype. Clin Cancer Res. 2009; 15:6412-20. doi: 10.1158/1078-0432.CCR-09-1438.
35. de Miranda NF, Goudkade D, Jordanova ES, Tops CM, Hes FJ, Vasen HF, van Wezel T, Morreau H. Infiltration of Lynch colorectal cancers by activated immune cells associates with early staging of the primary tumor and absence of lymph node metastases. Clin Cancer Res. 2012; 18:1237-45. doi: 10.1158/1078-0432.CCR-11-1997.
36. Balermpas P, Michel Y, Wagenblast J, Seitz O, Weiss C, Rödel F, Rödel C, Fokas E. Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer. Br J Cancer. 2014; 110:501-9. doi: 10.1038/bjc.2013.640.
37. Ward MJ, Thirdborough SM, Mellows T, Riley C, Harris S, Suchak K, Webb A, Hampton C, Patel NN, Randall CJ, Cox HJ, Jogai S, Primrose J, et al. Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer. Br J Cancer. 2014; 110:489-500. doi: 10.1038/bjc.2013.639.
38. 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; 88:223-30. doi: 10.1038/sj.bjc.6600694.
39. 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; 92:913-20. doi: 10.1038/sj.bjc.6602407.
40. Jie HB, Gildener-Leapman N, Li J, Srivastava RM, Gibson SP, Whiteside TL, Ferris RL. Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients. Br J Cancer. 2013; 109:2629-35. doi: 10.1038/bjc.2013.645.
41. Whiteside TL. What are regulatory T cells (Treg) regulating in cancer and why? Semin Cancer Biol. 2012; 22:327-34. doi: 10.1016/j.semcancer.2012.03.004.
42. Melero I, Hervas-Stubbs S, Glennie M, Pardoll DM, Chen L. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer. 2007; 7:95-106. doi: 10.1038/nrc2051.
43. Mueller SN, Ahmed R. High antigen levels are the cause of T cell exhaustion during chronic viral infection. Proc Natl Acad Sci USA. 2009; 106:8623-8. doi: 10.1073/pnas.0809818106.
44. Wherry EJ. T cell exhaustion. Nat Immunol. 2011; 12:492-9.
45. Yi JS, Cox MA, Zajac AJ. T-cell exhaustion: characteristics, causes and conversion. Immunology. 2010; 129:474-81. doi: 10.1111/j.1365-2567.2010.03255.x.
46. Jiang Y, Li Y, Zhu B. T-cell exhaustion in the tumor microenvironment. Cell Death Dis. 2015; 6: e1792. doi: 10.1038/cddis.2015.162.
47. Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N, Levionnois E, Nizard M, Si-Mohamed A, Besnier N, Gey A, Rotem-Yehudar R, Pere H, et al. PD-1-Expressing Tumor-Infiltrating T Cells Are a Favorable Prognostic Biomarker in HPV-Associated Head and Neck Cancer. Cancer Res. 2013; 73:128-38. doi: 10.1158/0008-5472.CAN-12-2606.
48. Partlová S, Boucek J, Kloudová K, Lukešová E, Zábrodskỳ M, Grega M, Fucíková J, Truxová I, Tachezy R, Špíšek R, Fialová A. 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: e965570. doi: 10.4161/21624011.2014.965570.
49. Lin YM, Sung WW, Hsieh MJ, Tsai SC, Lai HW, Yang SM, Shen KH, Chen MK, Lee H, Yeh KT, Chen CJ. High PD-L1 Expression Correlates with Metastasis and Poor Prognosis in Oral Squamous Cell Carcinoma. PLoS One. 2015; 10: e0142656. doi: 10.1371/journal.pone.0142656.
50. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373:123-35. doi: 10.1056/NEJMoa1504627.
51. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015; 373:23-34. doi: 10.1056/NEJMoa1504030.
52. Wansom D, Light E, Thomas D, Worden F, Prince M, Urba S, Chepeha D, Kumar B, Cordell K, Eisbruch A, Taylor J, Moyer J, Bradford C, et al. Infiltrating lymphocytes and human papillomavirus-16 associated oropharyngeal cancer. Laryngoscope. 2012; 122:121-7. doi: 10.1002/lary.22133.
53. Wansom D, Light E, Worden F, Prince M, Urba S, Chepeha DB, Cordell K, Eisbruch A, Taylor J, D'Silva N, Moyer J, Bradford CR, Kurnit 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; 136:1267-73. doi: 10.1001/archoto.2010.211.
54. Malm IJ, Bruno TC, Fu J, Zeng Q, Taube JM, Westra W, Pardoll D, Drake CG, Kim YJ. Expression profile and in vitro blockade of programmed death-1 in human papillomavirus-negative head and neck squamous cell carcinoma. Head Neck. 2015; 37:1088-95. doi: 10.1002/hed.23706.
55. Kim HS, Lee JY, Lim SH, Park K, Sun JM, Ko YH, Baek CH, Son Y, Jeong HS, Ahn YC, Lee MY, Hong M, Ahn MJ. Association Between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma. Cancer Res Treat. 2015; 48:527-36. doi: 10.4143/crt.2015.249.
56. Seiwert TY, Haddad RI, Gupta S, Mehra R, Tahara M, Berger R, Lee SH, Burtness B, Le DT, Heath K, Blum A, Dolled-Filhart M, Emancipator K, et al. Antitumor Activity of the Anti-PD-1 Antibody Pembrolizumab in Biomarker-Unselected Patients with R/M Head and Neck Cancer: Preliminary Results from KEYNOTE-012 Expansion Cohort. J Clin Oncol. 2015; 33:abstr LBA6008.
57. Kirilovsky A, Marliot F, El Sissy C, Haicheur N, Galon J, Pagès F. Rational bases for the use of the Immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients. Int Immunol. 2016; 28:20-40. doi: 10.1093/intimm/dxw021.
58. Junker N, Kvistborg P, Køllgaard T, Straten P thor, Andersen MH, Svane IM. Tumor associated antigen specific T-cell populations identified in ex vivo expanded TIL cultures. Cell Immunol. 2012; 273:1-9. doi: 10.1016/j.cellimm.2011.12.004.
59. Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014; 515:563-7. doi: 10.1038/nature14011.
60. Wieland U, Ritzkowsky A, Stoltidis M, Weissenborn S, Stark S, Ploner M, Majewski S, Jablonska S, Pfister HJ, Fuchs PG. Papillomavirus DNA in basal cell carcinomas of immunocompetent patients: an accidental association? J Invest Dermatol. 2000; 115:124-8. doi: 10.1046/j.1523-1747.2000.00015.x.
61. Goode A, Gilbert B, Harkes J, Jukic D, Satyanarayanan M. OpenSlide: A vendor-neutral software foundation for digital pathology. J Pathol Inform. 2013; 4: 27. doi: 10.4103/2153-3539.119005.
62. Martinez K, Cupitt J. VIPS-a highly tuned image processing software architecture. IEEE International Conference on Image Processing 2005. IEEE; 2005. p. II-574 doi: 10.1109/ICIP.2005.1530120.