CCL26-CX3CR1 Axis Mediates a Feedback Loop between Cancer Cell and PMN-MDSCs to Promote CD8⁺ T Cell Exhaustion during Stomach Carcinogenesis.

ABSTRACT: The development of an immunosuppressive microenvironment is a critical factor in stomach carcinogenesis. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) serve a pivotal function in mediating immune suppression. However, the precise mechanisms underlying PMN-MDSCs infiltration into the tumor immune microenvironment (TIME) and their immunosuppressive functions remain poorly understood. In this investigation, we observed that PMN-MDSCs were up-regulated during stomach carcinogenesis, with gastric cancer (GC) cells secreting CCL26 to promote the infiltration of PMN-MDSCs into the TIME via the CX3CR1 receptor. The infiltrating CX3CR1⁺ PMN-MDSCs secreted transforming growth factor-β1 (TGF-β1), which, through the SMAD2/3/SNAI1 signaling pathway, further sustained the sec

SUBMITTER: Jiang X 

PROVIDER: S-EPMC12635414 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature