title: A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17(+) cell frequency.
abstract: Patients with HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with non-HPV-induced OPSCC. The role of the immune response in this phenomenon is yet unclear. We studied the number of T cells, regulatory T cells (Tregs), T helper 17 (Th17) cells and IL-17(+) non-T cells (mainly granulocytes) in matched HPV-positive and HPV-negative OPSCC cases (n = 162). Furthermore, the production of IFN-γ and IL-17 by tumor-infiltrating T cells was analyzed. The number of tumor-infiltrating T cells and Tregs was higher in HPV-positive than HPV-negative OPSCC (p < 0.0001). In contrast, HPV-negative OPSCC contained significantly higher numbers of IL-17(+) non-T cells (p < 0.0001). Although a high number of intra-tumoral T cells showed a trend toward improved survival of all OPSCC patients, their prognostic effect in patients with a low number of intra-tumoral IL-17(+) non-T cells was significant with regard to disease-specific (p = 0.033) and disease-free survival (p = 0.012). This suggests that a high frequency of IL-17(+) non-T cells was related to a poor immune response, which was further supported by the observation that a high number of T cells was correlated with improved disease-free survival in the HPV-positive OPSCC (p = 0.008). In addition, we detected a minor Th17 cell population. However, T cells obtained from HPV-positive OPSCC produced significantly more IL-17 than those from HPV-negative tumors (p = 0.006). The improved prognosis of HPV-positive OPSCC is thus correlated with higher numbers of tumor-infiltrating T cells, more active Th17 cells and lower numbers of IL-17(+) non-T cells.
authors.affiliation: Department of Pathology, Leiden University Medical Center (LUMC), P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: Punt
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Emilie A C
authors.initials: EA
authors.lastname: Dronkers
authors.affiliation: Department of Clinical Oncology, LUMC, Leiden, The Netherlands.
authors.forename: Marij J P
authors.initials: MJ
authors.lastname: Welters
authors.affiliation: Department of Clinical Oncology, LUMC, Leiden, The Netherlands.
authors.forename: Renske
authors.initials: R
authors.lastname: Goedemans
authors.affiliation: Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Senada
authors.initials: S
authors.lastname: Koljenović
authors.affiliation: Department of Pathology, VU Medical Center (VUMC), Amsterdam, The Netherlands.|Department of Oral and Maxillofacial Surgery/Oral Pathology, Academic Centre for Dentistry, Amsterdam, The Netherlands.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bloemena
authors.affiliation: Department of Pathology, VU Medical Center (VUMC), Amsterdam, The Netherlands.
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.affiliation: Department of Pathology, Leiden University Medical Center (LUMC), P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Arko
authors.initials: A
authors.lastname: Gorter
authors.affiliation: Department of Clinical Oncology, LUMC, Leiden, The Netherlands.
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Baatenburg de Jong
authors.affiliation: Department of Pathology, Leiden University Medical Center (LUMC), P.O. Box 9600, 2300 RC, Leiden, The Netherlands. E.S.Jordanova@lumc.nl.|Center for Gynecological Oncology Amsterdam, VUMC, Amsterdam, The Netherlands. E.S.Jordanova@lumc.nl.
authors.forename: Ekaterina S
authors.initials: ES
authors.lastname: Jordanova
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D018655:Lymphocyte Count; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000150:complications / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17
keywords: Head and neck cancer; IL-17; T cell; Th17 cell; Treg; Tumor microenvironment