Hematopoietic Prostaglandin D2 Synthase Controls Tfh/Th2 Communication and Limits Tfh Antitumor Effects.
Fiche publication
Date publication
mai 2022
Journal
Cancer immunology research
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ARNOULD Laurent, Pr BERNARD Alain, Dr BOIDOT Romain, Pr GHIRINGHELLI François, Mme TRUNTZER Caroline, Dr VEGRAN Frédérique, Dr BRUCHARD Mélanie, Dr CHALMIN Fanny, Dr LIMAGNE Emeric, Dr DERANGERE Valentin, Dr THIBAUDIN Marion
Tous les auteurs :
Mary R, Chalmin F, Accogli T, Bruchard M, Hibos C, Melin J, Truntzer C, Limagne E, Derangère V, Thibaudin M, Humblin E, Boidot R, Chevrier S, Arnould L, Richard C, Klopfenstein Q, Bernard A, Urade Y, Harker JA, Apetoh L, Ghiringhelli F, Végran F
Lien Pubmed
Résumé
T follicular helper (Tfh) cells are a subset of CD4+ T cells essential in immunity and have a role in helping B cells produce antibodies against pathogens. However, their role during cancer progression remains unknown. The mechanism of action of Tfh cells remains elusive because contradictory data have been reported on their protumor or antitumor responses in human and murine tumors. Like Tfh cells, Th2 cells are also involved in humoral immunity and are regularly associated with tumor progression and poor prognosis, mainly through their secretion of IL4. Here, we showed that Tfh cells expressed hematopoietic prostaglandin D2 (PGD2) synthase in a pSTAT1/pSTAT3-dependent manner. Tfh cells produced PGD2, which led to recruitment of Th2 cells via the PGD2 receptor chemoattractant receptor homologous molecule expressed on Th type 2 cells (CRTH2) and increased their effector functions. This cross-talk between Tfh and Th2 cells promoted IL4-dependent tumor growth. Correlation between Th2 cells, Tfh cells, and hematopoietic PGD2 synthase was observed in different human cancers and associated with outcome. This study provides evidence that Tfh/Th2 cross-talk through PGD2 limits the antitumor effects of Tfh cells and, therefore, could serve as a therapeutic target.
Référence
Cancer Immunol Res. 2022 05 25;:OF1-OF17