Nature Immunology, Published online: 22 August 2025; doi:10.1038/s41590-025-02247-y

Using in vivo CRISPR–Cas9 screens of CD8+ T cells in a melanoma model, we identified STUB1 as an inhibitor of T cell-mediated antitumor immunity. STUB1 forms a complex with CHIC2, and together, they negatively regulate the expression of cytokine receptors, thereby limiting intratumoral CD8+ T cell numbers and function.



Summary

A study in Nature Immunology (August 2025) used CRISPR-Cas9 to screen CD8+ T cells in mice with melanoma, identifying STUB1 as a suppressor of anti-tumor immunity. The research revealed STUB1 forms a complex with CHIC2. This complex inhibits cytokine receptor expression, which in turn restricts the number and effectiveness of CD8+ T cells within the tumor microenvironment. These findings suggest targeting the STUB1-CHIC2 complex could be a potential strategy to enhance T cell-mediated cancer immunotherapy.

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