Senescent Tumor Cells Build a Cytokine Shield in Colorectal Cancer.

ABSTRACT: Cellular senescence can either support or inhibit cancer progression. Here, it is shown that intratumoral infiltration of CD8⁺ T cells is negatively associated with the proportion of senescent tumor cells in colorectal cancer (CRC). Gene expression analysis reveals increased expression of C-X-C motif chemokine ligand 12 (CXCL12) and colony stimulating factor 1 (CSF1) in senescent tumor cells. Senescent tumor cells inhibit CD8⁺ T cell infiltration by secreting a high concentration of CXCL12, which induces a loss of CXCR4 in T cells that result in impaired directional migration. CSF1 from senescent tumor cells enhance monocyte differentiation into M2 macrophages, which inhibit CD8⁺ T cell activation. Neutralization of CXCL12/CSF1 increases the effect of anti-

SUBMITTER: Choi YW 

PROVIDER: S-EPMC7887594 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature