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A STUB1-CHIC2 complex decreases IL-27Rα expression on CD8+ T cells to restrain tumor immunity [RNAseq_STUB1KO]

GSE294202 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/06/10 Platform GPL19057
Summary
In vivo CRISPR screens in CD8+ T cells have previously uncovered targets for cancer immunotherapy, yet they have not been used to compare the key regulators important at different stages of CD8+ T cell activation. Here we present two 899-gene in vivo CRISPR screens using naive or activated CD8+ T cells to address this gap. These screens identified the E3 ubiquitin ligase STUB1 as a novel negative regulator of anti-tumor CD8+ T cells. Stub1 knockout (KO) CD8+ T cells control tumor growth across multiple murine models. Mechanistically, STUB1 interacts with the adapter protein CHIC2 to regulate cytokine receptor expression in mouse and human CD8+ T cells. Among the cytokine receptors regulated by this complex, IL-27Ra is essential for Stub1/Chic2 KO-mediated tumor growth control. Together, these findings establish that the STUB1-CHIC2 complex as a novel regulator of cytokine receptor expression in CD8+ T cells and provide rationale for inhibiting this pathway to enhance CD8+ T cell-mediated anti-tumor immunity.
Published in
A STUB1-CHIC2 complex inhibits CD8(+) T cells to restrain tumor immunity
LaFleur MW, Milling LE, Prathima P et al. · Nature immunology 2025 · PMID 40796662 · doi:10.1038/s41590-025-02231-6
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Also filed as BioProject PRJNA1248550 and SRA study SRP577533. Searching any of these in the dataset finder brings you back here.

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