Evidence map›Paper›PMID 40506611›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2025

OTUD1 downregulates PD-L1 expression by deubiquitinating STAT3 and promotes the immune response in ccRCC.

Huaiyuan Liang, Xinlin Liu, Wanyang Guo, Wei Xiong, Da Ren, Wentao Liu

Abstract read
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

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0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Huaiyuan Liang *Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Xinlin Liu *Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Wanyang Guo *Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Wei XiongDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. xiongwei1404@126.com.
Da RenDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. 2008renda@csu.edu.cn.
Wentao LiuDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China. xyeyylwt@csu.edu.cn.

Funding

National Natural Science Youth Foundation of China 82203537Natural Science Foundation of Hunan Province 2022JJ40719Scientific Research Project of Hunan Provincial Health Commission B202304056613
6 · The paper itself

Abstract

backgroundClear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the urinary system and has the highest mortality rate. In addition to surgical tumor reduction, systemic drug therapy is the most important treatment method for metastatic renal cancer. In recent years, immunotherapeutic drugs represented by PD-1 antibodies have been used in the treatment of metastatic ccRCC and achieved good therapeutic effects. However, due to the occurrence of immune escape, only about 50-60% of patients with advanced renal cancer can significantly benefit from immunotherapy. The mechanism of immune escape is extremely complex and has not been clarified. We intend to delve into the driving mechanisms of immune evasion in ccRCC and explore potential targets for intervention.

methodsIn this study, we analyzed the expression of OTUD1 and related pathways in ccRCC through TCGA, GEO dataset, and cBioPortal web tool. At the same time, a mouse model of allogeneic transplanted clear cell renal cell carcinoma was constructed, and the effect of OTUD1 on anti-PD1 antibody therapy was discussed. Experiments such as co-IP, flow cytometry, and RNA-seq analysis were used to investigate the mechanism by which OTUD1 regulates immunity through STAT3.

resultsThis study reveals that OTUD1 suppresses PD-L1 expression and enhances antitumor immunity in clear cell renal cell carcinoma (ccRCC) by deubiquitinating and stabilizing STAT3, thereby inhibiting its nuclear translocation and transcriptional activity. As a key regulator of the JAK-STAT pathway, OTUD1 disrupts PD-1/PD-L1-mediated immune evasion, offering a potential therapeutic strategy to improve immunotherapy responses in ccRCC. These findings highlight the OTUD1-STAT3-PD-L1 axis as a novel mechanism for overcoming immune checkpoint resistance.

conclusionOverall, we demonstrate that OTUD1 interacts with STAT3 and deubiquitinates, inhibits its nuclear translocation and activity, and ultimately inhibits immune evasion of ccRCC by downregulating PD-L1.

Indexed as

B7-H1 AntigenCarcinoma, Renal CellDown-RegulationImmunityKidney NeoplasmsSTAT3 Transcription FactorUbiquitin-Specific ProteasesAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceUbiquitinationB7-H1 AntigenCD274 protein, humanSTAT3 protein, humanSTAT3 Transcription FactorUbiquitin-Specific ProteasesccRCCImmune responseOTUD1PD-L1STAT3

Identifiers

PMID40506611
PMCPMC12528312

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.