Macrophage-derived CCL5 facilitates immune escape of colorectal cancer cells via the p65/STAT3-CSN5-PD-L1 pathway.

ABSTRACT: Infiltrated macrophages are an important constituent of the tumor microenvironment and play roles in tumor initiation and progression by promoting immune evasion. However, the molecular mechanism by which macrophage-derived cytokines foster immune escape of colorectal cancer (CRC) is unclear. Here, we demonstrated that macrophage infiltration induced by lipopolysaccharide (LPS) or a high-cholesterol diet (HCD) significantly promoted CRC growth. Similarly, LPS and poly (I:C) remarkably increased the volume of CT26 cell allograft tumors. C-C motif chemokine ligand 5 (CCL5), which is secreted by macrophages, inhibited T-cell-mediated killing of HT29 cells and promoted immune escape by stabilizing PD-L1 in vitro and in vivo. Mechanistically, CCL5 resulted in formation of nuclear factor kappa-B

SUBMITTER: Liu C 

PROVIDER: S-EPMC7244707 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature