title: 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.affiliation: INSERM U970 PARCC, Sorbonne Paris-Cité, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Badoual
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hans
authors.forename: Nathalie
authors.initials: N
authors.lastname: Merillon
authors.forename: Cordélia
authors.initials: C
authors.lastname: Van Ryswick
authors.forename: Patrice
authors.initials: P
authors.lastname: Ravel
authors.forename: Nadine
authors.initials: N
authors.lastname: Benhamouda
authors.forename: Emeline
authors.initials: E
authors.lastname: Levionnois
authors.forename: Mevyn
authors.initials: M
authors.lastname: Nizard
authors.forename: Ali
authors.initials: A
authors.lastname: Si-Mohamed
authors.forename: Nicolas
authors.initials: N
authors.lastname: Besnier
authors.forename: Alain
authors.initials: A
authors.lastname: Gey
authors.forename: Rinat
authors.initials: R
authors.lastname: Rotem-Yehudar
authors.forename: Hélène
authors.initials: H
authors.lastname: Pere
authors.forename: Thi
authors.initials: T
authors.lastname: Tran
authors.forename: Coralie L
authors.initials: CL
authors.lastname: Guerin
authors.forename: Anne
authors.initials: A
authors.lastname: Chauvat
authors.forename: Estelle
authors.initials: E
authors.lastname: Dransart
authors.forename: Cécile
authors.initials: C
authors.lastname: Alanio
authors.forename: Sebastien
authors.initials: S
authors.lastname: Albert
authors.forename: Beatrix
authors.initials: B
authors.lastname: Barry
authors.forename: Federico
authors.initials: F
authors.lastname: Sandoval
authors.forename: Françoise
authors.initials: F
authors.lastname: Quintin-Colonna
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Wolf H
authors.initials: WH
authors.lastname: Fridman
authors.forename: Francois M
authors.initials: FM
authors.lastname: Lemoine
authors.forename: Stephane
authors.initials: S
authors.lastname: Oudard
authors.forename: Ludger
authors.initials: L
authors.lastname: Johannes
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
authors.forename: Daniel
authors.initials: D
authors.lastname: Brasnu
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D014408:Biomarkers, Tumor; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor