1. PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer
- Author
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Rinat Rotem-Yehudar, Patrick Bruneval, Cécile Alanio, Daniel Olive, Emeline Levionnois, Françoise Quintin-Colonna, Mevyn Nizard, Thi Tran, Wolf H. Fridman, Nathalie Merillon, Cordelia Van Ryswick, Hélène Péré, Coralie L. Guerin, François M. Lemoine, Alain Gey, Ludger Johannes, Cécile Badoual, Federico Sandoval, Ali Si-Mohamed, Eric Tartour, Nadine Benhamouda, Estelle Dransart, Stéphane Oudard, Nicolas Besnier, Stéphane Hans, Daniel Brasnu, Béatrix Barry, Patrice Ravel, Sebastien Albert, and Anne Chauvat
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,T-Lymphocytes ,Programmed Cell Death 1 Receptor ,Fluorescent Antibody Technique ,Lymphocyte Activation ,Flow cytometry ,Mice ,Immune system ,Lymphocytes, Tumor-Infiltrating ,T-Lymphocyte Subsets ,Internal medicine ,medicine ,Carcinoma ,Biomarkers, Tumor ,Tumor Microenvironment ,Animals ,Humans ,medicine.diagnostic_test ,business.industry ,Head and neck cancer ,Papillomavirus Infections ,Cancer ,FOXP3 ,medicine.disease ,Flow Cytometry ,Prognosis ,Blockade ,Mice, Inbred C57BL ,Head and Neck Neoplasms ,Carcinoma, Squamous Cell ,Female ,Cancer vaccine ,business - Abstract
Head and neck cancers positive for human papillomavirus (HPV) have a more favorable clinical outcome than HPV-negative cancers, but it is unknown why this is the case. We hypothesized that prognosis was affected by intrinsic features of HPV-infected tumor cells or differences in host immune response. In this study, we focused on a comparison of regulatory Foxp3+ T cells and programmed death-1 (PD-1)+ T cells in the microenvironment of tumors that were positive or negative for HPV, in two groups that were matched for various clinical and biologic parameters. HPV-positive head and neck cancers were more heavily infiltrated by regulatory T cells and PD-1+ T cells and the levels of PD-1+ cells were positively correlated with a favorable clinical outcome. In explaining this paradoxical result, we showed that these PD-1+ T cells expressed activation markers and were functional after blockade of the PD-1–PD-L1 axis in vitro. Approximately 50% of PD-1+ tumor-infiltrating T cells lacked Tim-3 expression and may indeed represent activated T cells. In mice, administration of a cancer vaccine increased PD-1 on T cells with concomitant tumor regression. In this setting, PD-1 blockade synergized with vaccine in eliciting antitumor efficacy. Our findings prompt a need to revisit the significance of PD-1–infiltrating T cells in cancer, where we suggest that PD-1 detection may reflect a previous immune response against tumors that might be reactivated by PD-1/PD-L1 blockade. Cancer Res; 73(1); 128–38. ©2012 AACR.
- Published
- 2012