Tranilast Inhibits the Function of Cancer‐Associated Fibroblasts Responsible for the Induction of Immune Suppressor Cell Types

Cancer‐associated fibroblasts ( CAF s) are the dominant stromal component in the tumour microenvironment ( TME ), playing critical roles in generation of pro‐tumourigenic TME ; however, their contribution to suppression of antitumour immune responses has not been fully understood. To elucidate the interaction between CAF s and immune suppressor cells, we examined whether inhibition of CAF s function would impair the induction of immune suppressor cell types in vitro . In this study, we applied an anti‐allergic and antifibrotic agent tranilast, which is used clinically, and evaluated a potential of tranilast to serve as a CAF s inhibitor. CAF s that had been isolated from E.G7 or LLC 1 tumour‐bearing mice were cultured in the presence of tranilast, and thereafter, CAF s functions on the secretion of some soluble factors as well as the induction of immune suppressor cells were evaluated. As a result, tranilast inhibited the proliferation of CAF s and reduced the levels of stromal cell‐derived factor‐1, prostaglandin E 2 and transforming growth factor‐ β 1 from CAF s in a dose‐dependent manner. On the other hand, tranilast exerted no inhibitory effects on immune cells at doses under 100  μ m . The induction of regulatory T cells and myeloid‐derived suppressor cells from their progenitor cells was suppressed in the medium that CAF s had been cultured in the presence of tranilast; however, these findings were not observed when those progenitor cells were cultured in the medium containing tranilast alone. These data demonstrate that tranilast inhibits CAF s function, which is responsible for the induction of immune suppressor cells, and possesses a potential to serve as a specific CAF s inhibitor.