Cgas deficiency promotes tumor growth by supporting B cell persistence and angiogenesis
Issued Date
2025-12-01
Resource Type
ISSN
00088749
eISSN
10902163
Scopus ID
2-s2.0-105017272940
Journal Title
Cellular Immunology
Volume
418
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cellular Immunology Vol.418 (2025)
Suggested Citation
Chantawichitwong P., Kumpunya S., Wongtangprasert T., Visitchanakun P., Pisitkun T., Pisitkun P. Cgas deficiency promotes tumor growth by supporting B cell persistence and angiogenesis. Cellular Immunology Vol.418 (2025). doi:10.1016/j.cellimm.2025.105036 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112435
Title
Cgas deficiency promotes tumor growth by supporting B cell persistence and angiogenesis
Corresponding Author(s)
Other Contributor(s)
Abstract
The 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<sup>−/−</sup> mice exhibited significantly larger tumors and reduced survival compared to WT mice. Tumors in Cgas<sup>−/−</sup> 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<sup>−/−</sup> mice showed an expansion of B cells, including regulatory B cells producing IL-10. B cells from tumor-bearing Cgas<sup>−/−</sup> 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<sup>−/−</sup> mice, where fibrosis and tumor vasculature persisted. Notably, despite B cell depletion, B cells remained in the tumors of Cgas<sup>−/−</sup> mice, in contrast to WT mice, where depletion correlated with increased CD8<sup>+</sup> T cell infiltration. Upregulation of Tgfb1, Tlr7, Tlr9, and Tnfrsf13c in tumors of Cgas<sup>−/−</sup> mice suggested a tumor microenvironment (TME) that promotes B cell survival. Furthermore, Cgas<sup>−/−</sup> 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<sup>−/−</sup> B cells enhance angiogenesis and are resistant to B cell depletion, contributing to tumor progression.