Evidence map›Paper›PMID 41023441›Full record

ArticleEMBO reports2025

The deubiquitinase USP17LA negatively regulates T-cell activation and attenuates anti-tumor immunity.

Huiling Zhang, Zhihan Guo, Gaigai Wei, Jingjing Yi, Zixi Wang, Yuqi Zhang, Haiping Zhao, Tingrong Ren, Yihan Wang, Jiating Kuang and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EMBO reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. [Ubiquitination-mediated regulation of T cell homeostasis and autoimmune diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Huiling Zhang *Children's Hospital of Fudan University, National Children's Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China.ORCID 0000-0002-5981-2404
Zhihan Guo *Children's Hospital of Fudan University, National Children's Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China.ORCID 0000-0002-8885-9383
Gaigai WeiInstitute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, 201102, Shanghai, China.ORCID 0000-0002-9026-7301
Jingjing YiInstitute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, 201102, Shanghai, China.
Zixi WangInstitute of Pediatrics, Children's Hospital of Fudan University, National Children's Medical Center, Fudan University, 201102, Shanghai, China.
Yuqi ZhangChildren's Hospital of Fudan University, National Children's Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China.
Haiping ZhaoChildren's Hospital of Fudan University, National Children's Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China.ORCID 0000-0002-3982-3624
Tingrong RenChildren's Hospital of Fudan University, National Children's Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China.ORCID 0000-0002-5415-7797
Yihan WangChildren's Hospital of Fudan University, National Children's Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China.
Jiating KuangChildren's Hospital of Fudan University, National Children's Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China.ORCID 0009-0004-4323-1973
Zhaoying ShengChildren's Hospital of Fudan University, National Children's Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China.
Duanwu ZhangChildren's Hospital of Fudan University, National Children's Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, 200032, Shanghai, China. duanwu@fudan.edu.cn.ORCID 0000-0003-2946-846X

Funding

MOST | National Natural Science Foundation of China (NSFC) 32370926MOST | National Natural Science Foundation of China (NSFC) 82071780Science and Technology Commission of Shanghai Municipality (STCSM) 21JC1400900
6 · The paper itself

Abstract

T-cell activation is essential for effective immune responses, yet its precise regulatory mechanisms remain incompletely understood. In this study, we show that the deubiquitinases of the Ubiquitin-Specific Peptidase 17-like (USP17L) family are significantly upregulated following T-cell stimulation. Using CRISPR-mediated gene knockout mice, we demonstrate that USP17LA, but not USP17LB, acts as a negative regulator of T-cell activation. Loss of Usp17la leads to increased production of pro-inflammatory cytokines, enhanced T-cell proliferation and effector functions, without affecting T-cell development or homeostasis. Furthermore, Usp17la deletion augments TCR signaling and anti-tumor immunity, improving T-cell-mediated tumor surveillance in murine tumor models. Mechanistically, proteomic analysis revealed that USP17LA strongly associates with cadherin-binding and calmodulin-binding pathways. Notably, USP17LA interacts with RACK1 and prevents its ubiquitin-dependent degradation, thereby promoting RACK1-mediated suppression of NFAT activity and the subsequent inhibition of T-cell function. These findings establish USP17LA as a pivotal modulator of T-cell activation and suggest that targeting USP17LA could enhance anti-tumor immunity, offering a potential strategy for cancer immunotherapy.

Indexed as

EndopeptidasesLymphocyte ActivationNeoplasmsT-LymphocytesAnimalsCell ProliferationCytokinesHumansMiceMice, KnockoutNFATC Transcription FactorsReceptors, Antigen, T-CellSignal TransductionCytokinesEndopeptidasesNFATC Transcription FactorsReceptors, Antigen, T-CellAnti-tumor ImmunityNFATRACK1T-cell ActivationUSP17LA

Identifiers

PMID41023441
PMCPMC12592519

What OpenQuestion holds

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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 OpenQuestion graph.