吡格列酮
兴奋剂
免疫疗法
结直肠癌
自噬
癌症研究
PD-L1
癌症免疫疗法
内科学
医学
癌症
受体
内分泌学
药理学
化学
生物化学
糖尿病
2型糖尿病
细胞凋亡
作者
Xiao Jia,Jing Qian,Huiqing Chen,Qian Liu,Shakeel Hussain,Jianhua Jin,Juanjuan Shi,Yongzhong Hou
标识
DOI:10.1016/j.ejphar.2023.175749
摘要
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.
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