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

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.

• Authors: 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
• Journal: Cancer research (Cancer Res) Vol. 73 Issue 1 Pg. 128-38 (Jan 01 2013) ISSN: 1538-7445 [Electronic] United States
• PMID: 23135914 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor

Topics

• Animals
• Biomarkers, Tumor (metabolism)
• Carcinoma, Squamous Cell (immunology, metabolism, virology)
• Female
• Flow Cytometry
• Fluorescent Antibody Technique
• Head and Neck Neoplasms (immunology, metabolism, virology)
• Humans
• Lymphocyte Activation (immunology)
• Lymphocytes, Tumor-Infiltrating (immunology, metabolism)
• Mice
• Mice, Inbred C57BL
• Papillomavirus Infections (complications, immunology, metabolism)
• Prognosis
• Programmed Cell Death 1 Receptor (biosynthesis, immunology)
• T-Lymphocyte Subsets (immunology)
• T-Lymphocytes (immunology)
• Tumor Microenvironment (immunology)