Loss of tumor intrinsic PD-L1 confers resistance to drug-induced apoptosis in human colon cancer

Colorectal cancer (CRC) with BRAF (V600E) is associated microsatellite instability (MSI) that predicts response to immune checkpoint inhibitors. We demonstrated the interrogation of TCGA RNA-seq human datasets revealed BRAFV600E tumors had significantly higher Programmed Death Ligand 1 (PD-L1) mRNA compared non-mutated CRCs. Also, MSI-H were evaluated as PD-L1 than MSS Inhibition MEK/ERK by cobimetinib or CDK inhibitor dinaciclib was shown attenuate mutant BRAF-induced coincident reduced c-JUN and YAP expression whose combined knockdown PD-L1. Using datasets, in colon cancers expression. The deletion can reduce tumor cell growth clonogenic assay. Analysis role a mediator chemosensitivity then performed. Knockout induction DNA double-strand breaks (pH2AX) caspase-3 cleavage 5-fluorouracil (5-FU) paclitaxel parental CRC cells. Results confirmed knockout MC38 murine cells where re-expression wild-type promoted damage apoptosis. also performed assay flow cytometry prove loss attenuated apoptosis induced diverse anti-cancer drugs could be reversed restoration Mechanistically, association reductions p-AKT BH3-only proteins BIM BIK, rather STAT3 However, significant melanoma, which shows heterogeneity cancers. In summary, upregulate c-jun enhance chemotherapy-induced Together, we demonstrate potential for regulator suppression confers chemoresistance. These findings expand understanding functions include nonimmune mechanisms suggest use biomarker cytotoxic chemotherapy.