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| Status |
Public on Jun 29, 2024 |
| Title |
EPDR1 promotes PD-L1 expression and antitumor immune evasion by inhibiting TRIM21-dependent ubiquitylation if IKBKB. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
While immune checkpoint blockade (ICB) has shown promise for clinical cancer therapy, its efficacy has only been observed in a limited subset of patients and the underlying mechanisms regulating innate and acquired resistance to ICB of tumor cells is poorly understood. Here, we identified EPDR1 as an important intrinsic tumor regulator of PD-L1 expression and the antitumor T-cell response that inhibits TRIM21-dependent ubiquitylation of IKBKB. Mechanistically, EPDR1 binds to TRIM21 and disrupts its interaction with IKBKB, which suppresses the ubiquitylation and autophagosome degradation of the IKBKB protein and thus enhances NF-κB-mediated transcriptional activation of PD-L1. We further confirmed through a mouse liver cancer model that EPDR1 mediates the exhaustion of CD8+ T cells and promotes tumor progression. In addition, we observed a positive correlation between EPDR1 and PD-L1 expression in both human and mouse liver cancer samples. Collectively, our study reveals an unappreciated role of EPDR1 in orchestrating tumor immune evasion and cancer progression, suggesting that targeting EPDR1-TRIM21 is a potential strategy for cancer immunotherapy.
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| Overall design |
To investigate the pathway that involved in the EPDR1 mediated regulation of PD-L1, we performed qRT‒PCR analyses on a series of immune-related molecules in HepG2 cells, HepG2 cells expressing NTC and shEPDR1 was collected and followed sequencing
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| Contributor(s) |
Qian X, Shen S |
| Citation(s) |
39152265 |
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| Submission date |
Dec 14, 2023 |
| Last update date |
Oct 15, 2024 |
| Contact name |
Xiaoyu Qian |
| E-mail(s) |
xiaoyu8274687@outlook.com
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| Organization name |
South China University of Technology
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| Street address |
Guangzhou Panyu University City
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| City |
Guangzhou |
| State/province |
Guangzhou |
| ZIP/Postal code |
510641 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA1052586 |
