A SENP7-SIRT1-IL-10 Axis Driven by DeSUMOylation Promotes Breg Differentiation and Immune Evasion in Colorectal Cancer.

ABSTRACT: Colorectal cancer (CRC) poses a significant global health challenge, yet immune checkpoint blockade (ICB) therapy benefits only a small subset of patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumours. Through analyses of public single-cell and spatial transcriptomic datasets, primary mouse cell sorting and adoptive transfer experiments, flow cytometry, multiplex immunofluorescence, immunohistochemistry, and coimmunoprecipitation, we revealed that sentrin-specific protease 7 (SENP7) promotes regulatory B-cell (Breg) differentiation and inhibits senescence by activating the expression of the NAD-dependent protein deacetylase sirtuin-1 (SIRT1) via deSUMOylation, thereby enhancing the expression of genes such as interleukin-10 (IL-10). Notably, targe

SUBMITTER: Liao Y 

PROVIDER: S-EPMC12681700 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature