Immune related proteins and tumor infiltrating CD8+ lymphocytes in hypopharyngeal cancer in relation to human papillomavirus (HPV) and clinical outcome.
CD8-positive lymphocytes
clinical outcome
human papillomavirus
hypopharyngeal cancer
protein expression
Journal
Head & neck
ISSN: 1097-0347
Titre abrégé: Head Neck
Pays: United States
ID NLM: 8902541
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
05
03
2020
revised:
17
05
2020
accepted:
16
06
2020
pubmed:
3
7
2020
medline:
22
6
2021
entrez:
3
7
2020
Statut:
ppublish
Résumé
Hypopharyngeal cancer (HPSCC) shows a poor clinical outcome, while HPSCC, caused by human papillomavirus (HPV), presents a better outcome. Here, HPCC, immune proteins, and tumor infiltrating CD8+ lymphocytes (CD8+ TILs) were evaluated in relation to HPV and outcome. Fresh frozen tissue from four HPV-positive HPSCC, 39 HPV-negative HPSCC, and normal samples were analyzed for protein expression by the Proseek immuno-oncology immunoassay. CD8+ TIL numbers evaluated by immunohistochemistry on 144 formalin-fixed biopsies were analyzed in relation to clinical outcome. Proteins differing between HPV-positive and negative HPSCC included CD8A, PD-L1, Fas ligand, and chemokines. High CD8+ TIL numbers were correlated to improve clinical outcome in HPV-negative HPSCC. High expression of immune proteins in HPV-positive HPSCC may explain the better clinical outcome. CD8+ TILs are of relevance for outcome of HPV-negative HPSCC, while tumors with high immune activity but poor patient survival suggest a role for immune therapy.
Sections du résumé
BACKGROUND
Hypopharyngeal cancer (HPSCC) shows a poor clinical outcome, while HPSCC, caused by human papillomavirus (HPV), presents a better outcome. Here, HPCC, immune proteins, and tumor infiltrating CD8+ lymphocytes (CD8+ TILs) were evaluated in relation to HPV and outcome.
METHODS
Fresh frozen tissue from four HPV-positive HPSCC, 39 HPV-negative HPSCC, and normal samples were analyzed for protein expression by the Proseek immuno-oncology immunoassay. CD8+ TIL numbers evaluated by immunohistochemistry on 144 formalin-fixed biopsies were analyzed in relation to clinical outcome.
RESULTS
Proteins differing between HPV-positive and negative HPSCC included CD8A, PD-L1, Fas ligand, and chemokines. High CD8+ TIL numbers were correlated to improve clinical outcome in HPV-negative HPSCC.
CONCLUSIONS
High expression of immune proteins in HPV-positive HPSCC may explain the better clinical outcome. CD8+ TILs are of relevance for outcome of HPV-negative HPSCC, while tumors with high immune activity but poor patient survival suggest a role for immune therapy.
Substances chimiques
B7-H1 Antigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3206-3217Informations de copyright
© 2020 The Authors. Head & Neck published by Wiley Periodicals LLC.
Références
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
Che J, Wang Y, Zhang X, Chen J. Comparative efficacy of six therapies for hypopharyngeal and laryngeal neoplasms: a network meta-analysis. BMC Cancer. 2019;19(1):282.
IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Personal Habits and Indoor Combustions. Lyon, France: WHO; 2012.
Ramqvist T, Dalianis T. Oropharyngeal cancer epidemic and human papillomavirus. Emerg Infect Dis. 2010;16(11):1671-1677.
de Sanjose S, Serrano B, Tous S, et al. Burden of human papillomavirus (HPV)-related cancers attributable to HPVs 6/11/16/18/31/33/45/52 and 58. JNCI Cancer Spectr. 2018;2(4):pky045.
Haeggblom L, Attoff T, Hammarstedt-Nordenvall L, Nasman A. Human papillomavirus and survival of patients per histological subsite of tonsillar squamous cell carcinoma. Cancer Med. 2018;7(5):1717-1722.
Timbang MR, Sim MW, Bewley AF, Farwell DG, Mantravadi A, Moore MG. HPV-related oropharyngeal cancer: a review on burden of the disease and opportunities for prevention and early detection. Hum Vaccin Immunother. 2019;15(7-8):1920-1928.
Castellsague X, Alemany L, Quer M, et al. HPV involvement in head and neck cancers: comprehensive assessment of biomarkers in 3680 patients. J Natl Cancer Inst. 2016;108(6):djv403.
Ndiaye C, Mena M, Alemany L, et al. HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis. Lancet Oncol. 2014;15(12):1319-1331.
Wendt M, Romanitan M, Nasman A, et al. Presence of human papillomaviruses and p16 expression in hypopharyngeal cancer. Head Neck. 2014;36(1):107-112.
Dalianis T, Grun N, Koch J, et al. Human papillomavirus DNA and p16(INK4a) expression in hypopharyngeal cancer and in relation to clinical outcome, in Stockholm, Sweden. Oral Oncol. 2015;51(9):857-861.
Smeets SJ, Hesselink AT, Speel EJ, et al. A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen. Int J Cancer. 2007;121(11):2465-2472.
Joo YH, Lee YS, Cho KJ, et al. Characteristics and prognostic implications of high-risk HPV-associated hypopharyngeal cancers. PLoS One. 2013;8(11):e78718.
Hughes RT, Beuerlein WJ, O'Neill SS, et al. Human papillomavirus-associated squamous cell carcinoma of the larynx or hypopharynx: clinical outcomes and implications for laryngeal preservation. Oral Oncol. 2019;98:20-27.
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.
Nordfors C, Grun N, Tertipis N, 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(11):2522-2530.
Oguejiofor K, Hall J, Slater C, et al. Stromal infiltration of CD8 T cells is associated with improved clinical outcome in HPV-positive oropharyngeal squamous carcinoma. Br J Cancer. 2015;113(6):886-893.
Keck MK, Zuo Z, Khattri A, et al. Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes. Clin Cancer Res. 2015;21(4):870-881.
Ward MJ, Thirdborough SM, Mellows T, et al. Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer. Br J Cancer. 2014;110(2):489-500.
Ono T, Azuma K, Kawahara A, et al. Pre-treatment CD8(+) tumour-infiltrating lymphocyte density predicts distant metastasis after definitive treatment in patients with stage III/IV hypopharyngeal squamous cell carcinoma. Clin Otolaryngol. 2018;43(5):1312-1320.
Ono T, Azuma K, Kawahara A, et al. Association between PD-L1 expression combined with tumor-infiltrating lymphocytes and the prognosis of patients with advanced hypopharyngeal squamous cell carcinoma. Oncotarget. 2017;8(54):92699-92714.
Chen X, Wang J, Wang R, et al. Th1-, Th2-, and Th17-associated cytokine expression in hypopharyngeal carcinoma and clinical significance. Eur Arch Otorhinolaryngol. 2016;273(2):431-438.
Birtalan E, Danos K, Gurbi B, et al. Expression of PD-L1 on immune cells shows better prognosis in laryngeal, Oropharygeal, and Hypopharyngeal cancer. Appl Immunohistochem Mol Morphol. 2018;26(7):e79-e85.
Schneider S, Kadletz L, Wiebringhaus R, et al. PD-1 and PD-L1 expression in HNSCC primary cancer and related lymph node metastasis - impact on clinical outcome. Histopathology. 2018;73(4):573-584.
Katayama A, Takahara M, Kishibe K, et al. Expression of B7-H3 in hypopharyngeal squamous cell carcinoma as a predictive indicator for tumor metastasis and prognosis. Int J Oncol. 2011;38(5):1219-1226.
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.
Ramqvist T, Nasman A, Franzen B, et al. Protein expression in tonsillar and base of tongue cancer and in relation to human papillomavirus (HPV) and clinical outcome. Int J Mol Sci. 2018;19(4);978:1-17.
Assarsson E, Lundberg M, Holmquist G, et al. Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability. PLoS One. 2014;9(4):e95192.
Benjamini Y, Hochberg Y. Controlling the false discovery rate - a practical and powerful approach to multiple testing. J Roy Stat Soc B Met. 1995;57(1):289-300.
Franzen B, Alexeyenko A, Kamali-Moghaddam M, et al. Protein profiling of fine-needle aspirates reveals subtype-associated immune signatures and involvement of chemokines in breast cancer. Mol Oncol. 2019;13(2):376-391.
Franzen B, Kamali-Moghaddam M, Alexeyenko A, et al. A fine-needle aspiration-based protein signature discriminates benign from malignant breast lesions. Mol Oncol. 2018;12(9):1415-1428.
Coppola D, Nebozhyn M, Khalil F, et al. Unique ectopic lymph node-like structures present in human primary colorectal carcinoma are identified by immune gene array profiling. Am J Pathol. 2011;179(1):37-45.
Prabhakaran S, Rizk VT, Ma Z, et al. Evaluation of invasive breast cancer samples using a 12-chemokine gene expression score: correlation with clinical outcomes. Breast Cancer Res. 2017;19(1):71.
Messina JL, Fenstermacher DA, Eschrich S, et al. 12-chemokine gene signature identifies lymph node-like structures in melanoma: potential for patient selection for immunotherapy? Sci Rep. 2012;2:765.
Partlova S, Boucek J, Kloudova 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. Onco Targets Ther. 2015;4(1):e965570.
Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1-10.
Oguejiofor K, Galletta-Williams H, Dovedi SJ, Roberts DL, Stern PL, West CM. Distinct patterns of infiltrating CD8+ T cells in HPV+ and CD68 macrophages in HPV-oropharyngeal squamous cell carcinomas are associated with better clinical outcome but PD-L1 expression is not prognostic. Oncotarget. 2017;8(9):14416-14427.
Wansom D, Light E, Thomas D, et al. Infiltrating lymphocytes and human papillomavirus-16-associated oropharyngeal cancer. Laryngoscope. 2012;122(1):121-127.
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.
de Ruiter EJ, de Roest RH, Brakenhoff RH, et al. Digital pathology-aided assessment of tumor-infiltrating T lymphocytes in advanced stage, HPV-negative head and neck tumors. Cancer Immunol Immunother. 2020;69:581-591.
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.
Huang Z, Xie N, Liu H, et al. The prognostic role of tumour-infiltrating lymphocytes in oral squamous cell carcinoma: a meta-analysis. J Oral Pathol Med. 2019;48(9):788-798.
Hoesli R, Birkeland AC, Rosko AJ, et al. Proportion of CD4 and CD8 tumor infiltrating lymphocytes predicts survival in persistent/recurrent laryngeal squamous cell carcinoma. Oral Oncol. 2018;77:83-89.