title: Human ectonucleotidase-expressing CD25highTh17 cells accumulate in breast cancer tumors and exert immunosuppressive functions.
abstract: Th17 cells contribute to the development of some autoimmune and allergic diseases by driving tissue inflammation. However, the function of Th17 cells during cancer progression remains controversial. Here, we show that human memory CD25highTh17 cells suppress T cell immunity in breast cancer. Ectonucleotidase-expressing Th17 cells accumulated in breast cancer tumors and suppressed CD4+and CD8+T cell activation. These cells expressed both Rorγt and Foxp3 genes and secreted Th17 related cytokines. We further found that CD39 ectonucleotisase expression on tumor-infiltrating Th17 cells was driven by TGF-βand IL-6. Finally, immunohistochemical analysis of localized breast cancer revealed that high-tumor infiltration by IL-17+cells was associated with a poor clinical outcome and impeded the favorable effect of high CD8+infiltration. Altogether, these findings suggest that intratumoral Th17 cells compromise anticancer immune responses in breast cancer patients.
authors.affiliation: UMR866; INSERM; Dijon, France; Faculté de Médecine; Université de Bourgogne; Dijon, France; MT and MC share first co-authorship.
authors.forename: Marion
authors.initials: M
authors.lastname: Thibaudin
authors.affiliation: Department of Medical Oncology; Centre Georges François Leclerc; Dijon, France; MT and MC share first co-authorship.
authors.forename: Marie
authors.initials: M
authors.lastname: Chaix
authors.affiliation: UMR866; INSERM; Dijon, France; Faculté de Médecine; Université de Bourgogne; Dijon, France; Department of Medical Oncology; Centre Georges François Leclerc; Dijon, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Boidot
authors.affiliation: UMR866; INSERM; Dijon, France; Faculté de Médecine; Université de Bourgogne; Dijon, France; Department of Medical Oncology; Centre Georges François Leclerc; Dijon, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Végran
authors.affiliation: UMR866; INSERM; Dijon, France; Faculté de Médecine; Université de Bourgogne; Dijon, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: Derangère
authors.affiliation: UMR866; INSERM; Dijon, France; Faculté de Médecine; Université de Bourgogne; Dijon, France.
authors.forename: Emeric
authors.initials: E
authors.lastname: Limagne
authors.affiliation: UMR866; INSERM; Dijon, France; Faculté de Médecine; Université de Bourgogne; Dijon, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Berger
authors.affiliation: UMR866; INSERM; Dijon, France; Faculté de Médecine; Université de Bourgogne; Dijon, France; Department of Medical Oncology; Centre Georges François Leclerc; Dijon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladoire
authors.affiliation: UMR866; INSERM; Dijon, France; Faculté de Médecine; Université de Bourgogne; Dijon, France; Department of Medical Oncology; Centre Georges François Leclerc; Dijon, France; LA and FG share senior co-authorship.
authors.forename: Lionel
authors.initials: L
authors.lastname: Apetoh
authors.affiliation: UMR866; INSERM; Dijon, France; Faculté de Médecine; Université de Bourgogne; Dijon, France; Department of Medical Oncology; Centre Georges François Leclerc; Dijon, France; LA and FG share senior co-authorship.
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
keywords: Th17; breast cancer; ectonucleotidase; prognosis