A noncanonical function of SCIMP restricts JAK1 activity to counteract immune evasion in bladder cancer
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ABSTRACT: Despite the fact that immunotherapy is reshaping the therapeutic landscape of bladder cancer, immune evasion remains a major obstacle to durable clinical benefit. In this study, we performed a genome-wide CRISPR-Cas9 screen in bladder cancer cells co-cultured with CD8⁺ T cells and identified SCIMP as a key gene that enhances CD8⁺ T cell antitumor immunity. SCIMP serves as a favorable prognostic biomarker in bladder cancer patients treated with immunotherapy. Mechanistically, SCIMP inhibits JAK1 phosphorylation in an adaptor-independent manner, suppressing IFN-γ/JAK1/STAT5A/PD-L1 signaling axis. Meanwhile, YTHDF2 destabilizes the m6A tagged SCIMP transcripts. Remarkably, SCIMP synergizes with PD-1 blockade in suppressing tumor growth. Collectively, these findings reveal a previously unexplored noncanonical role of SCIMP in preventing immune evasion and provide a potential therapeutic target for bladder cancer.
ORGANISM(S): Homo sapiens
PROVIDER: GSE320572 | GEO | 2026/03/05
REPOSITORIES: GEO
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