PD1-Infiltrating T Cells: A Good Prognostic Biomarker in HPV Associated Head and Neck Cancer
Cecile Badoual, Stephane Hans, Nathalie Merillon, Patrice Ravel, Nadine Benhamouda, Emeline Levionnois, Mevyn Nizard, Ali Si Mohamed, Patrick Bruneval, Daniel Olive, Daniel Brasnu, Eric Tartour. INSERM U970 PARCC, Paris, France; Hôpital Européen G Pompidou, Paris, France
Background: The mechanisms underlying the more favorable outcome of HPV-associated head and neck cancer have not been elucidated. This better prognosis may reflect intrinsic features of HPV infected tumor cells or differences in host immune response.
Design: We compared the tumor microenvironment of 32 HPV-positive and 32 HPV-negative head and neck cancers focusing on immunosuppressive cells (regulatory Foxp3+ T cells and PD-1+T cells). These two groups were matched for various parameters Double immunofluroescence staining and multiparametric cytometry were selected to quantitate immune cells in tumor.
Results: We found that HPV-associated head and neck cancers were associated with a better prognosis compared to HPV negative tumors. They were more heavily infiltrated by regulatory T cells and PD-1 expressing T cells. Surprisingly, levels of PD-1+T cell infiltration were positively correlated with a favorable clinical outcome in HPV- associated head and neck cancers. To explain this paradoxical result, we showed that these PD-1+T cells expressed markers of activation and were functional in vitro after blockade of the PD-1-PDL-1 axis. One half of PD-1 positive tumor-infiltrating T cells did not express Tim-3 and may represent indeed activated T cells. In addition, in mice, we showed that cancer vaccine increased PD-1 on T cells and concomitantly induced tumor regression. PD-1 blockade synergized with vaccine efficacy.
Conclusions: This study therefore revisits the significance of PD-1-infiltrating T cells in cancer. We provide arguments showing that PD-1 detection could reflect a past anti-tumor immune response, which could be reactivated by PD-1/PD-L1 blockade.
Category: Head & Neck
Monday, March 4, 2013 1:45 PM
Proffered Papers: Section F, Monday Afternoon