Abstract
Blockade of PD-1/PD-L1 immune checkpoint could be an effective antitumor strategy for multiple types of cancer, but it is low response rate for colorectal cancer patients with unclear mechanism. Here we found that PPARγ agonist pioglitazone could reduce PD-L1 protein levels without effect on its gene expression. Further analysis showed that pioglitazone induced PD-L1 autophagic degradation in a PPARγ-dependent manner. Pioglitazone promoted PD-L1 translocation to lysosome by immunofluorescence analysis, which was associated with the increased binding of PPARγ to PD-L1. Moreover the combined pioglitazone with PD-1 antibody enhanced colorectal tumor immunotherapy, which was involved in reduced PD-L1 levels and increased CD8+ T cells. These findings suggest that PPARγ agonist could induce PD-L1 autophagic degradation resulting in increased colorectal tumor immunotherapy.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
