Distinct patterns of intratumoral immune cell infiltrates in patients with HPV-associated compared to non-virally induced head and neck squamous cell carcinoma
Status PubMed-not-MEDLINE Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25949860
PubMed Central
PMC4368144
DOI
10.4161/21624011.2014.965570
PII: 965570
Knihovny.cz E-zdroje
- Klíčová slova
- CD8+ T lymphocytes, Cox-2, cyclooxygenase 2, HNSCC, HNSCC, head and neck squamous cell carcinoma, HPV, HPV, human papillomavirus, PD-1, PD-1, programmed cell death 1, PD-L1, programmed cell death-ligand 1, Tim-3, Tim-3, T cell immunoglobulin and mucin protein 3, Treg, regulatory T cell, mDC, myeloid dendritic cell, pDC, plasmacytoic dendritic cell,
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Human papillomavirus (HPV) infection is one of the most important etiologic causes of oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients with HPV-positive HNSCC were reported to have a better clinical outcome than patients with HPV-negative cancers. However, little is known about the possible causes of different clinical outcomes. In this study, we analyzed a detailed immune profile of tumor samples from HNSCC patients with respect to their HPV status. We analyzed the characteristics of immune cell infiltrates, including the frequency and distribution of antigen-presenting cells and naïve, regulatory and effector T cells and the cytokine and chemokine levels in tumor tissue. There was a profound difference in the extent and characteristics of intratumoral immune cell infiltrates in HNSCC patients based on their HPV status. In contrast to HPV-negative tumor tissues, HPV-positive tumor samples showed significantly higher numbers of infiltrating IFNγ+ CD8+ T lymphocytes, IL-17+ CD8+ T lymphocytes, myeloid dendritic cells and proinflammatory chemokines. Furthermore, HPV-positive tumors had significantly lower expression of Cox-2 mRNA and higher expression of PD1 mRNA compared to HPV-negative tumors. The presence of a high level of intratumoral immune cell infiltrates might play a crucial role in the significantly better response of HPV-positive patients to standard therapy and their favorable clinical outcome. Furthermore, characterization of the HNSCC immune profile might be a valuable prognostic tool in addition to HPV status and might help identify novel targets for therapeutic strategies, including cancer immunotherapy.
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Nasman A, Attner P, Hammarstedt L, Du J, Eriksson M, Giraud G, Ahrlund-Richter S, Marklund L, Romanitan M, Lindquist D, et al. Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer 2009; 125:362-6; PMID:; http://dx.doi.org/10.1002/ijc.24339 PubMed DOI
Lajer CB, von Buchwald C. The role of human papillomavirus in head and neck cancer. APMIS 2010; 118:510-9; PMID:; http://dx.doi.org/10.1111/j.1600-0463.2010.02624.x PubMed DOI
Licitra L, Perrone F, Bossi P, Suardi S, Mariani L, Artusi R, Oggionni M, Rossini C, Cantu G, Squadrelli M, et al. High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol 2006; 24:5630-6; PMID:; http://dx.doi.org/10.1200/JCO.2005.04.6136 PubMed DOI
Lassen P, Eriksen JG, Hamilton-Dutoit S, Tramm T, Alsner J, Overgaard J. Effect of HPV-associated p16INK4 A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol 2009; 27:1992-8; PMID:; http://dx.doi.org/10.1200/JCO.2008.20.2853 PubMed DOI
Spanos WC, Nowicki P, Lee DW, Hoover A, Hostager B, Gupta A, Anderson ME, Lee JH. Immune response during therapy with cisplatin or radiation for human papillomavirus-related head and neck cancer. Arch Otolaryngol Head Neck Surg 2009; 135:1137-46; PMID:; http://dx.doi.org/10.1001/archoto.2009.159 PubMed DOI
Kimple RJ, Harari PM, Torres AD, Yang RZ, Soriano BJ, Yu M, Armstrong EA, Blitzer GC, Smith MA, Lorenz LD, et al. Development and characterization of HPV-positive and HPV-negative head and neck squamous cell carcinoma tumorgrafts. Clin Cancer Res 2013; 19:855-64; PMID:; http://dx.doi.org/10.1158/1078-0432.CCR-12-2746 PubMed DOI PMC
Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313:1960-4; PMID:; http://dx.doi.org/10.1126/science.1129139 PubMed DOI
Clemente CG, Mihm MC, Jr, Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 1996; 77:1303-10; PMID:; http://dx.doi.org/10.1002/(SICI)1097-0142(19960401)77:7%3c1303::AID-CNCR12%3e3.0.CO;2-5 PubMed DOI
Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA 2005; 102:18538-43; PMID:; http://dx.doi.org/10.1073/pnas.0509182102 PubMed DOI PMC
Kocian P, Sedivcova M, Drgac J, Cerna K, Hoch J, Kodet R, Bartunkova J, Spisek R, Fialova A. Tumor-infiltrating lymphocytes and dendritic cells in human colorectal cancer: their relationship to KRAS mutational status and disease recurrence. Hum Immunol 2011; 72:1022-8; PMID:; http://dx.doi.org/10.1016/j.humimm.2011.07.312 PubMed DOI
Kawai O, Ishii G, Kubota K, Murata Y, Naito Y, Mizuno T, Aokage K, Saijo N, Nishiwaki Y, Gemma A, et al. Predominant infiltration of macrophages and CD8(+) T Cells in cancer nests is a significant predictor of survival in stage IV nonsmall cell lung cancer. Cancer 2008; 113:1387-95; PMID:; http://dx.doi.org/10.1002/cncr.23712 PubMed DOI
Wansom D, Light E, Worden F, Prince M, Urba S, Chepeha DB, Cordell K, Eisbruch A, Taylor J, D’Silva N, 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; PMID:; http://dx.doi.org/10.1001/archoto.2010.211 PubMed DOI PMC
Nasman A, Romanitan M, Nordfors C, Grun N, Johansson H, Hammarstedt L, Marklund L, Munck-Wikland E, Dalianis T, Ramqvist T. Tumor infiltrating CD8+ and Foxp3 +lymphocytes correlate to clinical outcome and human papillomavirus (HPV) status in tonsillar cancer. PLoS One 2012; 7:e38711; PMID:; http://dx.doi.org/10.1371/journal.pone.0038711 PubMed DOI PMC
Nordfors C, Grun N, Tertipis N, Ahrlund-Richter A, Haeggblom L, Sivars L, Du J, Nyberg T, Marklund L, Munck-Wikland E, et al. CD8(+) and CD4(+) tumour infiltrating lymphocytes in relation to human papillomavirus status and clinical outcome in tonsillar and base of tongue squamous cell carcinoma. Eur J Cancer 2013; 49:2522-30; PMID:; http://dx.doi.org/10.1016/j.ejca.2013.03.019 PubMed DOI
Fialova A, Partlova S, Sojka L, Hromadkova H, Brtnicky T, Fucikova J, Kocian P, Rob L, Bartunkova J, Spisek R. Dynamics of T-cell infiltration during the course of ovarian cancer: the gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T-cells. Int J Cancer 2013; 132:1070-9; PMID:; http://dx.doi.org/10.1002/ijc.27759 PubMed DOI
Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ohtani H. CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 1998; 58:3491-4; PMID: PubMed
Hasmim M, Badoual C, Vielh P, Drusch F, Marty V, Laplanche A, de Oliveira Diniz M, Roussel H, De Guillebon E, Oudard S, et al. Expression of EPHRIN-A1, SCINDERIN and MHC class I molecules in head and neck cancers and relationship with the prognostic value of intratumoral CD8+ T cells. BMC Cancer 2013; 13:592; PMID:; http://dx.doi.org/10.1186/1471-2407-13-592 PubMed DOI PMC
Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N, Levionnois E, Nizard M, Si-Mohamed A, Besnier 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; 73:128-38; PMID:; http://dx.doi.org/10.1158/0008-5472.CAN-12-2606 PubMed DOI
Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004; 10:942-9; PMID:; http://dx.doi.org/10.1038/nm1093 PubMed DOI
Miracco C, Mourmouras V, Biagioli M, Rubegni P, Mannucci S, Monciatti I, Cosci E, Tosi P, Luzi P. Utility of tumour-infiltrating CD25+FOXP3+ regulatory T cell evaluation in predicting local recurrence in vertical growth phase cutaneous melanoma. Oncol Rep 2007; 18:1115-22; PMID:; http://dx.doi.org/10.3892/or.18.5.1115 PubMed DOI
Bohling SD, Allison KH. Immunosuppressive regulatory T cells are associated with aggressive breast cancer phenotypes: a potential therapeutic target. Mod Pathol 2008; 21:1527-32; PMID:; http://dx.doi.org/10.1038/modpathol.2008.160 PubMed DOI
Hiraoka N, Onozato K, Kosuge T, Hirohashi S. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res 2006; 12:5423-34; PMID:; http://dx.doi.org/10.1158/1078-0432.CCR-06-0369 PubMed DOI
Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, Platell C, Iacopetta B. Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol 2009; 27:186-92; PMID:; http://dx.doi.org/10.1200/JCO.2008.18.7229 PubMed DOI
Alvaro T, Lejeune M, Salvado MT, Bosch R, Garcia JF, Jaen J, Banham AH, Roncador G, Montalban C, Piris MA. Outcome in Hodgkin's lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells. Clin Cancer Res 2005; 11:1467-73; PMID:; http://dx.doi.org/10.1158/1078-0432.CCR-04-1869 PubMed DOI
Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay Nel H, Mosseri V, Laccourreye O, Bruneval P, Fridman WH, et al. Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res 2006; 12:465-72; PMID:; http://dx.doi.org/10.1158/1078-0432.CCR-05-1886 PubMed DOI
Bron L, Jandus C, Andrejevic-Blant S, Speiser DE, Monnier P, Romero P, Rivals JP. Prognostic value of arginase-II expression and regulatory T-cell infiltration in head and neck squamous cell carcinoma. Int J Cancer 2013; 132:E85-93; PMID:; http://dx.doi.org/10.1002/ijc.27728 PubMed DOI
Loose D, Signore A, Bonanno E, Vermeersch H, Dierckx R, Deron P, Van de Wiele C. Prognostic value of CD25 expression on lymphocytes and tumor cells in squamous-cell carcinoma of the head and neck. Cancer Biother Radiopharm 2008; 23:25-33; PMID:; http://dx.doi.org/10.1089/cbr.2007.0373 PubMed DOI
Boucek J, Mrkvan T, Chovanec M, Kuchar M, Betka J, Boucek V, Hladikova M, Betka J, Eckschlager T, Rihova B. Regulatory T cells and their prognostic value for patients with squamous cell carcinoma of the head and neck. J Cell Mol Med 2010; 14:426-33; PMID:; http://dx.doi.org/10.1111/j.1582-4934.2008.00650.x PubMed DOI PMC
Heusinkveld M, Goedemans R, Briet RJ, Gelderblom H, Nortier JW, Gorter A, Smit VT, Langeveld AP, Jansen JC, van der Burg SH. Systemic and local human papillomavirus 16-specific T-cell immunity in patients with head and neck cancer. Int J Cancer 2012; 131:E74-85; PMID:; http://dx.doi.org/10.1002/ijc.26497 PubMed DOI
Piersma SJ, Welters MJ, van der Hulst JM, Kloth JN, Kwappenberg KM, Trimbos BJ, Melief CJ, Hellebrekers BW, Fleuren GJ, Kenter GG, et al. Human papilloma virus specific T cells infiltrating cervical cancer and draining lymph nodes show remarkably frequent use of HLA-DQ and -DP as a restriction element. Int J Cancer 2008; 122:486-94; PMID:; http://dx.doi.org/10.1002/ijc.23162 PubMed DOI
Welters MJ, Kenter GG, Piersma SJ, Vloon AP, Lowik MJ, Berends-van der Meer DM, Drijfhout JW, Valentijn AR, Wafelman AR, Oostendorp J, et al. Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine. Clin Cancer Res 2008; 14:178-87; PMID:; http://dx.doi.org/10.1158/1078-0432.CCR-07-1880 PubMed DOI
Marcus B, Arenberg D, Lee J, Kleer C, Chepeha DB, Schmalbach CE, Islam M, Paul S, Pan Q, Hanash S, et al. Prognostic factors in oral cavity and oropharyngeal squamous cell carcinoma. Cancer 2004; 101:2779-87; PMID:; http://dx.doi.org/10.1002/cncr.20701 PubMed DOI
Lam-ubol A, Hopkin D, Letuchy EM, Kurago ZB. Squamous carcinoma cells influence monocyte phenotype and suppress lipopolysaccharide-induced TNF-alpha in monocytes. Inflammation 2010; 33:207-23; PMID:; http://dx.doi.org/10.1007/s10753-009-9175-6 PubMed DOI PMC
Tan TT, Coussens LM. Humoral immunity, inflammation and cancer. Curr Opin Immunol 2007; 19:209-16; PMID:; http://dx.doi.org/10.1016/j.coi.2007.01.001 PubMed DOI
Ziegler-Heitbrock L. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J Leukoc Biol 2007; 81:584-92; PMID:; http://dx.doi.org/10.1189/jlb.0806510 PubMed DOI
Ramanathapuram LV, Hopkin D, Kurago ZB. Dendritic Cells (DC) facilitate detachment of squamous carcinoma cells (SCC), while SCC promote an immature CD16(+) DC phenotype and control DC migration. Cancer Microenviron 2013; 6:41-55; PMID:; http://dx.doi.org/10.1007/s12307-011-0077-4 PubMed DOI PMC
Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001; 410:50-6; PMID:; http://dx.doi.org/10.1038/35065016 PubMed DOI
Cojoc M, Peitzsch C, Trautmann F, Polishchuk L, Telegeev GD, Dubrovska A. Emerging targets in cancer management: role of the CXCL12CXCR4 axis. Onco Targets Ther 2013; 6:1347-61; PMID:; http://dx.doi.org/10.2147/OTT.S36109 PubMed DOI PMC
Alferink J, Lieberam I, Reindl W, Behrens A, Weiss S, Huser N, Gerauer K, Ross R, Reske-Kunz AB, Ahmad-Nejad P, et al. Compartmentalized production of CCL17 in vivo: strong inducibility in peripheral dendritic cells contrasts selective absence from the spleen. J Exp Med 2003; 197:585-99; PMID:; http://dx.doi.org/10.1084/jem.20021859 PubMed DOI PMC
Gupta RA, Dubois RN. Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 2001; 1:11-21; PMID:; http://dx.doi.org/10.1038/35094017 PubMed DOI
Howe LR, Subbaramaiah K, Brown AM, Dannenberg AJ. Cyclooxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer 2001; 8:97-114; PMID:; http://dx.doi.org/10.1677/erc.0.0080097 PubMed DOI
Ristimaki A, Sivula A, Lundin J, Lundin M, Salminen T, Haglund C, Joensuu H, Isola J. Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res 2002; 62:632-5; PMID: PubMed
Melero I, Hervas-Stubbs S, Glennie M, Pardoll DM, Chen L. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer 2007; 7:95-106; PMID:; http://dx.doi.org/10.1038/nrc2051 PubMed DOI
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; PMID:; http://dx.doi.org/10.1073/pnas.0809818106 PubMed DOI PMC
Yi JS, Cox MA, Zajac AJ. T-cell exhaustion: characteristics, causes and conversion. Immunology 2010; 129:474-81; PMID:; http://dx.doi.org/10.1111/j.1365-2567.2010.03255.x PubMed DOI PMC
Wherry EJ. T cell exhaustion. Nat Immunol 2011; 12:492-9; PMID:; http://dx.doi.org/10.1038/ni.2035 PubMed DOI
Gao X, Zhu Y, Li G, Huang H, Zhang G, Wang F, Sun J, Yang Q, Zhang X, Lu B. TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression. PLoS One 2012; 7:e30676; PMID:; http://dx.doi.org/10.1371/journal.pone.0030676 PubMed DOI PMC
Yang ZZ, Grote DM, Ziesmer SC, Niki T, Hirashima M, Novak AJ, Witzig TE, Ansell SM. IL-12 upregulates TIM-3 expression and induces T cell exhaustion in patients with follicular B cell non-Hodgkin lymphoma. J Clin Invest 2012; 122:1271-82; PMID:; http://dx.doi.org/10.1172/JCI59806 PubMed DOI PMC
Koslabova E, Hamsikova E, Salakova M, Klozar J, Foltynova E, Salkova E, Rotnaglova E, Ludvikova V, Tachezy R. Markers of HPV infection and survival in patients with head and neck tumors. Int J Cancer 2013; 133:1832-9; PMID:; http://dx.doi.org/10.1002/ijc.28194 PubMed DOI
Rotnaglova E, Tachezy R, Salakova M, Prochazka B, Kosl’abova E, Vesela E, Ludvikova V, Hamsikova E, Klozar J. HPV involvement in tonsillar cancer: prognostic significance and clinically relevant markers. Int J Cancer 2011; 129:101-10; PMID:; http://dx.doi.org/10.1002/ijc.25889 PubMed DOI
Klozar J, Kratochvil V, Salakova M, Smahelova J, Vesela E, Hamsikova E, Betka J, Tachezy R. HPV status and regional metastasis in the prognosis of oral and oropharyngeal cancer. Eur Arch Otorhinolaryngol 2008; 265 Suppl 1:S75-82; PMID:; http://dx.doi.org/10.1007/s00405-007-0557-9 PubMed DOI
Tachezy R, Klozar J, Salakova M, Smith E, Turek L, Betka J, Kodet R, Hamsikova E. HPV and other risk factors of oral cavityoropharyngeal cancer in the Czech Republic. Oral Dis 2005; 11:181-5; PMID:; http://dx.doi.org/10.1111/j.1601-0825.2005.01112.x PubMed DOI
van den Brule AJ, Pol R, Fransen-Daalmeijer N, Schouls LM, Meijer CJ, Snijders PJ. GP5+6 +PCR followed by reverse line blot analysis enables rapid and high-throughput identification of human papillomavirus genotypes. J Clin Microbiol 2002; 40:779-87; PMID:; http://dx.doi.org/10.1128/JCM.40.3.779-787.2002 PubMed DOI PMC
Gravitt PE, Peyton C, Wheeler C, Apple R, Higuchi R, Shah KV. Reproducibility of HPV 16 and HPV 18 viral load quantitation using TaqMan real-time PCR assays. J Virol Methods 2003; 112:23-33; PMID:; http://dx.doi.org/10.1016/S0166-0934(03)00186-1 PubMed DOI
Smeets SJ, Hesselink AT, Speel EJ, Haesevoets A, Snijders PJ, Pawlita M, Meijer CJ, Braakhuis BJ, Leemans CR, Brakenhoff RH. A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer 2007; 121:2465-72; PMID:; http://dx.doi.org/10.1002/ijc.22980 PubMed DOI
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