A beneficial tumor microenvironment in oropharyngeal squamous cell carcinoma is characterized by a high T cell and low IL-17^sup +^ cell frequency

• Published in: Cancer immunology, immunotherapy Vol. 65; no. 4; p. 393
• Main Authors: Punt, Simone, Dronkers, Emilie A; C, Welters, Marij J; P, Goedemans, Renske, Koljenovic, Senada, Bloemena, Elisabeth, Snijders, Peter J; F, Gorter, Arko, van der Burg, Sjoerd H, de Jong, Robert J; Baatenburg, Jordanova, Ekaterina S
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer Nature B.V 01.04.2016
• Subjects: Granulocytes; Head & neck cancer; Human papillomavirus; Lymphocytes; Medical prognosis; Oncology; Otolaryngology; Pathology; Tumors; Netherlands
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-016-1805-x

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^sup +^ 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^sup +^ 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^sup +^ 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^sup +^ 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^sup +^ non-T cells.