PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-Associated head and neck cancer

Cécile Badoual, Stéphane Hans, Nathalie Merillon, Cordéli Van Ryswick, Patrice Ravel, Nadine Benhamouda, Emeline Levionnois, Mevyn Nizard, Ali Si-Mohamed, Nicolas Besnier, Alain Gey, Rinat Rotem-Yehudar, Hél̀ene Pere, Thi Tran, Coralie L. Guerin, Anne Chauvat, Estelle Dransart, Cécile Alanio, Sebastien Albert, Beatrix BarryFederico Sandoval, Françoise Quintin-Colonna, Patrick Bruneval, Wolf H. Fridman, Francois M. Lemoine, Stephane Oudard, Ludger Johannes, Daniel Olive, Daniel Brasnu, Eric Tartour

Résultats de recherche: Contribution à un journalArticleRevue par des pairs

537 Citations (Scopus)

Résumé

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.

langue originaleAnglais
Pages (de - à)128-138
Nombre de pages11
journalCancer Research
Volume73
Numéro de publication1
Les DOIs
étatPublié - 1 janv. 2013
Modification externeOui

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