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Peer-reviewedCC BY-NC 4.0Journal for Immunotherapy of Cancer

Non-canonical function of SCIMP restricts JAK1 activity to counteract immune evasion in bladder cancer

  • Yongqiang You1
  • Hui Zhang1,2
  • Jiayin Sun1
  • Yujun Shuai3,4
  • Xin Shi1
  • Ye Yuan1
  • Sijia Hong1
  • Ning Wang1
  • Miao Wang1
  • Liang Wang1
  • Chao Huang1
  • Guosong Jiang1
4 affiliations
  1. 1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
  2. 2Hubei Key Laboratory of Regenerative Medicine and Multi-disciplinary Translational Research, Huazhong University of Science and Technology, Wuhan, Hubei, China
  3. 3Department of Urology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
  4. 4Institute of Urologic Science and Technology, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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Abstract

Background: Despite the fact that immunotherapy is reshaping the therapeutic landscape of bladder cancer, immune evasion remains a major obstacle to durable clinical benefit. Therefore, elucidating the mechanisms underlying immune resistance is essential for developing novel therapeutic strategies.

Methods: In this study, we performed a genome-wide CRISPR-Cas9 screen in bladder cancer cells co-cultured with CD8+ T cells and identified the SLP adaptor and CSK-interacting membrane protein (SCIMP) as a key gene that enhances CD8+ T cell antitumor immunity.

Results: SCIMP serves as a favorable prognostic biomarker in patients with bladder cancer treated with immunotherapy. Mechanistically, SCIMP restricts JAK1 phosphorylation in an adaptor-independent manner, suppressing the IFN-γ/JAK1/STAT5A/PD-L1 signaling axis. Meanwhile, YTHDF2 destabilizes the m6A-tagged SCIMP transcripts to reduce their expression. Remarkably, SCIMP synergizes with PD-1 blockade in suppressing tumor growth.

Conclusions: Collectively, these findings reveal a previously unexplored non-canonical role of SCIMP in preventing immune evasion and provide a potential therapeutic target for bladder cancer.

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Cite

BibTeXRIS
BibTeX
@article{you2026noncanonical,
  title = {{Non-canonical function of SCIMP restricts JAK1 activity to counteract immune evasion in bladder cancer}},
  author = {Yongqiang You and Hui Zhang and Jiayin Sun and Yujun Shuai and Xin Shi and Ye Yuan and Sijia Hong and Ning Wang and Miao Wang and Liang Wang and Chao Huang and Guosong Jiang},
  journal = {Journal for Immunotherapy of Cancer},
  year = {2026},
  month = oct,
  doi = {10.1136/jitc-2026-015651},
  url = {https://doi.org/10.1136/jitc-2026-015651},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Non-canonical function of SCIMP restricts JAK1 activity to counteract immune evasion in bladder cancer
AU  - Yongqiang You
AU  - Hui Zhang
AU  - Jiayin Sun
AU  - Yujun Shuai
AU  - Xin Shi
AU  - Ye Yuan
AU  - Sijia Hong
AU  - Ning Wang
AU  - Miao Wang
AU  - Liang Wang
AU  - Chao Huang
AU  - Guosong Jiang
PY  - 2026
DA  - 2026/10/27
JO  - Journal for Immunotherapy of Cancer
DO  - 10.1136/jitc-2026-015651
UR  - https://doi.org/10.1136/jitc-2026-015651
AB  - Background: Despite the fact that immunotherapy is reshaping the therapeutic landscape of bladder cancer, immune evasion remains a major obstacle to durable clinical benefit. Therefore, elucidating the mechanisms underlying immune resistance is essential for developing novel therapeutic strategies.  Methods: In this study, we performed a genome-wide CRISPR-Cas9 screen in bladder cancer cells co-cultured with CD8+ T cells and identified the SLP adaptor and CSK-interacting membrane protein (SCIMP) as a key gene that enhances CD8+ T cell antitumor immunity.  Results: SCIMP serves as a favorable prognostic biomarker in patients with bladder cancer treated with immunotherapy. Mechanistically, SCIMP restricts JAK1 phosphorylation in an adaptor-independent manner, suppressing the IFN-γ/JAK1/STAT5A/PD-L1 signaling axis. Meanwhile, YTHDF2 destabilizes the m6A-tagged SCIMP transcripts to reduce their expression. Remarkably, SCIMP synergizes with PD-1 blockade in suppressing tumor growth.  Conclusions: Collectively, these findings reveal a previously unexplored non-canonical role of SCIMP in preventing immune evasion and provide a potential therapeutic target for bladder cancer.
SN  - 2051-1426
ER  -