GSK0660 enhances antitumor immunotherapy by reducing PD-L1 expression

Blockade of PD-1/PD-L1 immune checkpoint is wildly used for multiple types of cancer treatment, while the low response rate for patients is still completely unknown. As nuclear hormone receptor, PPARδ (peroxisome-proliferator-activated receptor) regulates cell proliferation, inflammation, and tumor...

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Bibliographic Details
Published in:European journal of pharmacology 2024-06, Vol.972, p.176565-176565, Article 176565
Main Authors: Khan, Bibimaryam, Chen, Mingjun, Wang, Huijie, Khan, Afrasyab, Hussain, Shakeel, Shi, Juanjuan, Yang, Limin, Hou, Yongzhong
Format: Article
Language:English
Subjects:
Colon cancer
GSK0660
Immune escape
Immunotherapy
PD-L1
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Summary:Blockade of PD-1/PD-L1 immune checkpoint is wildly used for multiple types of cancer treatment, while the low response rate for patients is still completely unknown. As nuclear hormone receptor, PPARδ (peroxisome-proliferator-activated receptor) regulates cell proliferation, inflammation, and tumor progression, while the effect of PPARδ on tumor immune escape is still unclear. Here we found that PPARδ antagonist GSK0660 significantly reduced colon cancer cell PD-L1 protein and gene expression. Luciferase analysis showed that GSK0660 decreased PD-L1 gene transcription activity. Moreover, reduced PD-L1 expression in colon cancer cells led to increased T cell activity. Further analysis showed that GSK0660 decreased PD-L1 expression in a PPARδ dependent manner. Implanted tumor model analysis showed that GSK0660 inhibited tumor immune escape and the combined PD-1 antibody with GSK0660 effectively enhanced colorectal cancer immunotherapy. These findings suggest that GSK0660 treatment could be an effective strategy for cancer immunotherapy.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2024.176565