First Author | Cen B | Year | 2021 |
Journal | Oncogene | Volume | 40 |
Issue | 41 | Pages | 5984-5992 |
PubMed ID | 34385594 | Mgi Jnum | J:312450 |
Mgi Id | MGI:6790371 | Doi | 10.1038/s41388-021-01972-6 |
Citation | Cen B, et al. (2021) Mutant APC promotes tumor immune evasion via PD-L1 in colorectal cancer. Oncogene 40(41):5984-5992 |
abstractText | PD-L1 expression is elevated in various human cancers, including colorectal cancer. High levels of PD-L1 expressed on tumor epithelial cells are one of the potential mechanisms by which tumor cells become resistant to immune attack. However, PD-L1 regulation in tumor cells is not fully understood. Here we demonstrate that mutations in the adenomatous polyposis coli (APC) gene lead to colonic epithelial cell resistance to CD8(+) T cell cytotoxicity by induction of PD-L1 expression. Mechanistically, this occurs as a result of the beta-catenin/TCF4 complex binding to the PD-L1 promoter, leading to increased transcription. Our findings not only reveal a novel mechanism by which APC mutations induce tumor immune evasion via an immune checkpoint pathway but also pave the way for developing beta-catenin or TCF4 inhibitors as possible new options for immune checkpoint inhibition. |