Downregulated Smad3 signaling impairs the maturation of MO-MDSC in colorectal cancer.

ABSTRACT: Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immunosuppressive cells that expand in tumors due to impaired differentiation into macrophages (MΦ), dendritic cells (DC), or granulocytes. Despite extensive research, the mechanisms governing their differentiation remain incompletely understood. Transforming growth factor β1 (Tgfβ1), abundant in the tumor microenvironment (TME), regulates cellular differentiation via the classical Smad2/3 pathway, yet paradoxically fails to drive MDSC maturation. In this study, we demonstrate that Smad3 is significantly downregulated in MDSC from colorectal cancer (CRC) patients and tumor-bearing mouse models, impairing monocytic lineage maturation. Myeloid-specific Smad3 overexpression promotes the differentiation of MO-MDSC into mature

SUBMITTER: Li M 

PROVIDER: S-EPMC12686534 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature