A protective cGAMP-mediated anti-tumor immune response can proceed without LRRC8/VRAC channels.

ABSTRACT: The volume-regulated anion channel (VRAC) is a hetero-hexamer composed of LRRC8A and any of the four other LRRC8 paralogs (LRRC8B-E). Depending on their subunit composition, VRACs not only transport chloride, but also a range of organic substrates including 2'3'-cGAMP (cGAMP). Transfer of this immunomodulator from tumor to host cells is critical for antitumor immunity. Whether this process depends on VRAC in vivo remains incompletely understood. To address this issue, we studied subcutaneous MC38 and B16-F10 tumors in syngeneic mice. Enhanced growth of MC38 tumors lacking cGAMP production confirmed the importance of tumor-produced cGAMP. The impact of VRAC-mediated cGAMP-efflux from tumor cells and its uptake into cells of the tumor microenvironment was investigated using LRRC8A-deficient

SUBMITTER: Thone FMB 

PROVIDER: S-EPMC12828768 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature