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

Abstract

<div>Abstract<p>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<sup>+</sup> T cells and programmed death-1 (PD-1)<sup>+</sup> 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<sup>+</sup> T cells and the levels of PD-1<sup>+</sup> cells were positively correlated with a favorable clinical outcome. In explaining this paradoxical result, we showed that these PD-1<sup>+</sup> T cells expressed activation markers and were functional after blockade of the PD-1–PD-L1 axis <i>in vitro</i>. Approximately 50% of PD-1<sup>+</sup> 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. <i>Cancer Res; 73(1); 128–38. ©2012 AACR</i>.</p></div>