Hematopoietic Prostaglandin D2 Synthase Controls Tfh/Th2 Communication and Limits Tfh Antitumor Effects

T follicular helper (Tfh) cells are a subset of CD4 thorn 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 D-2 (PGD(2)) synthase in a pSTAT1/pSTAT3-dependent manner. Tfh cells produced PGD(2), which led to recruitment of Th2 cells via the PGD(2) 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 PGD(2) synthase was observed in different human cancers and associated with outcome. This study provides evidence that Tfh/Th2 cross-talk through PGD(2 )limits the antitumor effects of Tfh cells and, therefore, could serve as a therapeutic target.

Automated summary

The interaction between T follicular helper (Tfh) cells and Th2 cells through PGD(2) promotes tumor growth, indicating the significant role of Tfh/Th2 cell crosstalk in tumor progression.