TY - JOUR
T1 - PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-Associated head and neck cancer
AU - Badoual, Cécile
AU - Hans, Stéphane
AU - Merillon, Nathalie
AU - Van Ryswick, Cordéli
AU - Ravel, Patrice
AU - Benhamouda, Nadine
AU - Levionnois, Emeline
AU - Nizard, Mevyn
AU - Si-Mohamed, Ali
AU - Besnier, Nicolas
AU - Gey, Alain
AU - Rotem-Yehudar, Rinat
AU - Pere, Hél̀ene
AU - Tran, Thi
AU - Guerin, Coralie L.
AU - Chauvat, Anne
AU - Dransart, Estelle
AU - Alanio, Cécile
AU - Albert, Sebastien
AU - Barry, Beatrix
AU - Sandoval, Federico
AU - Quintin-Colonna, Françoise
AU - Bruneval, Patrick
AU - Fridman, Wolf H.
AU - Lemoine, Francois M.
AU - Oudard, Stephane
AU - Johannes, Ludger
AU - Olive, Daniel
AU - Brasnu, Daniel
AU - Tartour, Eric
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84871966600&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-12-2606
DO - 10.1158/0008-5472.CAN-12-2606
M3 - Article
C2 - 23135914
AN - SCOPUS:84871966600
SN - 0008-5472
VL - 73
SP - 128
EP - 138
JO - Cancer Research
JF - Cancer Research
IS - 1
ER -