Loss of DUSP6 Upregulates PD-L1 on Extracellular Vesicles

초록

Background: Tumor cells evade immune surveillance by upregulating the surface expression of programmed death-ligand 1(PD-L1), which interacts with programmed death-1 (PD-1) receptor on T cells to inhibits the anti-cancer immune response. The abundance of programmed death-ligand 1 on extracellular vesicles derived from cancer cells plays a role in immune escape by reducing T-cell activity and promoting tumor growth. Material and methods : We applied the CRISPR-Cas9 technology to target DUSP6 gene at the DNA level in mouse CT26 colon cancer cell lines. Extracellular vesicles from cell culture-conditioned medium were isolated by ultracentrifugation. The exosomal markers and PD-L1 in the extracellular vesicles were examined by western blotting. We also examined the tumorigenesis and growth of mouse CT26 colon cancer cell lines in syngeneic Balb/c mice. Results : We found that the PD-L1 on extracellular vesicles from DUSP6 knockout CT26 cells was higher than that from wildtype CT26 cells. In addition, DUSP6 knockout CT26 tumor grew markedly faster than wildtype CT26 cells. Conclusions : Our data suggest that DUSP6 is involved in the up-regulation of PD-L1 on extracellular vesicles derived from mouse CT26 colon cancer cell lines, and thus may play a major role in tumor growth and tumor immune evasion.