Chantawichitwong P.Kumpunya S.Wongtangprasert T.Visitchanakun P.Pisitkun T.Pisitkun P.Mahidol University2025-10-042025-10-042025-12-01Cellular Immunology Vol.418 (2025)00088749https://repository.li.mahidol.ac.th/handle/123456789/112435The cGAS sensor activates the STING/IFN signaling pathway, which is crucial for antiviral and antitumor responses. This study aims to investigate the cGAS-mediated immune responses in tumorigenesis using the MC-38 tumor model. MC38-tumor models were established in wild-type (WT) and Cgas-deficient mice to investigate immunophenotypes and cellular mechanisms involved in tumor progression. Cgas^−/− mice exhibited significantly larger tumors and reduced survival compared to WT mice. Tumors in Cgas^−/− mice showed increased fibrosis and neovascularity. WT mice mounted a more robust T-cell-mediated antitumor response, with higher levels of NK and effector T cells, while Cgas^−/− mice showed an expansion of B cells, including regulatory B cells producing IL-10. B cells from tumor-bearing Cgas^−/− mice demonstrated enhanced survival in the tumor-conditioned medium than those from WT mice. B cell depletion significantly reduced tumor size in WT mice but had minimal effect in Cgas^−/− mice, where fibrosis and tumor vasculature persisted. Notably, despite B cell depletion, B cells remained in the tumors of Cgas^−/− mice, in contrast to WT mice, where depletion correlated with increased CD8⁺ T cell infiltration. Upregulation of Tgfb1, Tlr7, Tlr9, and Tnfrsf13c in tumors of Cgas^−/− mice suggested a tumor microenvironment (TME) that promotes B cell survival. Furthermore, Cgas^−/− B cells promoted angiogenesis, as indicated by enhanced endothelial tube formation. cGAS deficiency fosters tumor growth by reducing the antitumor response, promoting a pro-tumor microenvironment, and supporting B cell survival. The Cgas^−/− B cells enhance angiogenesis and are resistant to B cell depletion, contributing to tumor progression.Immunology and MicrobiologyArticleSCOPUS10.1016/j.cellimm.2025.1050362-s2.0-10501727294010902163