Intratumoral HPV16-specific T cells constitute a type I–oriented tumor microenvironment to improve survival in HPV16-driven oropharyngeal cancer

Marij J.P. Welters, Wenbo Ma, Saskia J.A.M. Santegoets, Renske Goedemans, Ilina Ehsan, Ekaterina S. Jordanova, Vanessa J. Van Ham, Vincent Van Unen, Frits Koning, Sylvia I. Van Egmond, Pornpimol Charoentong, Zlatko Trajanoski, Lilly Ann Van Der Velden, Sjoerd H. Van Der Burg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Purpose: Human papillomavirus (HPV)–associated oropharyngeal squamous cell cancer (OPSCC) has a much better prognosis than HPV-negative OPSCC, and this is linked to dense tumor immune infiltration. As the viral antigens may trigger potent immunity, we studied the relationship between the presence of intratumoral HPV-specific T-cell responses, the immune contexture in the tumor microenvironment, and clinical outcome. Experimental Design: To this purpose, an in-depth analysis of tumor-infiltrating immune cells in a prospective cohort of 97 patients with HPV16-positive and HPV16-negative OPSCC was performed using functional T-cell assays, mass cytometry (CyTOF), flow cytometry, and fluorescent immunostaining of tumor tissues. Key findings were validated in a cohort of 75 patients with HPV16-positive OPSCC present in the publicly available The Cancer Genome Atlas database. Results: In 64% of the HPV16-positive tumors, type I HPV16-specific T cells were present. Their presence was not only strongly related to a better overall survival, a smaller tumor size, and less lymph node metastases but also to a type I–oriented tumor microenvironment, including high numbers of activated CD161þ T cells, CD103þ tissue-resident T cells, dendritic cells (DC), and DC-like macrophages. Conclusions: The viral antigens trigger a tumor-specific T-cell response that shapes a favorable immune contexture for the response to standard therapy. Hence, reinforcement of HPV16-specific T-cell reactivity is expected to boost this process.

Original languageEnglish
Pages (from-to)634-647
Number of pages14
JournalClinical Cancer Research
Issue number3
Publication statusPublished - 1 Feb 2018

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