Hematopoietic Prostaglandin D2Synthase Controls Tfh/Th2 Communication and Limits Tfh Antitumor Effects

Romain Mary, Fanny Chalmin, Théo Accogli, Mélanie Bruchard, Christophe Hibos, Joséphine Melin, Caroline Truntzer, Emeric Limagne, Valentin Derangère, Marion Thibaudin, Etienne Humblin, Romain Boidot, Sandy Chevrier, Laurent Arnould, Corentin Richard, Quentin Klopfenstein, Antoine Bernard, Yoshihiro Urade, James A. Harker, Lionel ApetohFrançois Ghiringhelli, Frédérique Végran

Research output: Contribution to journalArticlepeer-review

Abstract

T follicular helper (Tfh) cells are a subset ofCD4+ 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.

Original languageEnglish
Pages (from-to)900-916
Number of pages17
JournalCancer Immunology Research
Volume10
Issue number7
DOIs
StatePublished - Jul 2022

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