Inhibition of PCSK9 enhances the antitumor effect of PD-1 inhibitor in colorectal cancer by promoting the infiltration of CD8⁺ T cells and the exclusion of Treg cells.

ABSTRACT: Immunotherapy especially immune checkpoint inhibitors (ICIs) has brought favorable clinical results for numerous cancer patients. However, the efficacy of ICIs in colorectal cancer (CRC) is still unsatisfactory due to the poor median progression-free survival and overall survival. Here, based on the CRC models, we tried to elucidate novel relapse mechanisms during anti-PD-1 therapy. We found that PD-1 blockade elicited a mild antitumor effect in these tumor models with both increased CD8⁺ T cells and Treg cells. Gene mapping analysis indicated that proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor, transforming growth factor-β (TGF-β), and CD36 were unexpectedly upregulated during PD-1 blockade. To investigate the critical role of these prot

SUBMITTER: Wang R 

PROVIDER: S-EPMC9393481 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature