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Supplementary Figure 3 from PD-1–Expressing Tumor-Infiltrating T Cells Are a Favorable Prognostic Biomarker in HPV-Associated Head and Neck Cancer

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posted on 2023-03-30, 21:50 authored by Cécile Badoual, Stéphane Hans, Nathalie Merillon, Cordélia Van Ryswick, Patrice Ravel, Nadine Benhamouda, Emeline Levionnois, Mevyn Nizard, Ali Si-Mohamed, Nicolas Besnier, Alain Gey, Rinat Rotem-Yehudar, Hélène Pere, Thi Tran, Coralie L. Guerin, Anne Chauvat, Estelle Dransart, Cécile Alanio, Sebastien Albert, Beatrix Barry, Federico Sandoval, Françoise Quintin-Colonna, Patrick Bruneval, Wolf H. Fridman, Francois M. Lemoine, Stephane Oudard, Ludger Johannes, Daniel Olive, Daniel Brasnu, Eric Tartour

PDF file - 2.6MB, Relationship between tumor infiltration with Foxp3 regulatory T cells and survival

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ARTICLE 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.

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