PPAR agonist inhibits c-Myc-mediated colorectal cancer tumor immune escape

As a master transcription factor, c-Myc plays an important role in promoting tumor immune escape. In addition, PPAR? (peroxisome proliferator-activated receptor ?) regulates cell metabolism, inflammation, and tumor progression, while the effect of PPAR? on c-Myc-mediated tumor immune escape is still unclear. Here we found that cells treated with PPAR? agonist pioglitazone (PIOG) reduced c-Myc protein expression in a PPAR?-dependent manner. qPCR analysis showed that PIOG had no significant effect on c-Myc gene levels. Further analysis showed that PIOG decreased c-Myc protein half-life. Moreover, PIOG increased the binding of c-Myc to PPAR?, and induced c-Myc ubiquitination and degradation. Importantly, c-Myc increased PD-L1 and CD47 immune checkpoint protein expression and promoted tumor immune escape, while PIOG inhibited this event. These findings suggest that PPAR? agonist inhibited c-Myc-mediated tumor immune escape by inducing its ubiquitination and degradation.