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Co-culture CRISPR screens reveal ATG9A as a regulator to macrophage-mediated cytotoxicity in cancer

GSE266329 Mus musculus; Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2025/04/30 Platform GPL34328Platform GPL24676
Summary
This study investigates the role of cancer cell surface proteins in modulating the response of cancer cells to macrophage-induced cytotoxicity. Utilizing two targeted CRISPR screens using OVCAR-8 cell line and a targeted CRISPR library for cancer cell surface proteins, ATG9A was identified as a key regulator. ATG9A KO increased the sensitivity of cancer cells to macrophage-induced cytotoxicity. Subsequent RNA sequencing and other analysis elucidated the underlying mechanisms; ATG9A KO in cancer cells not only enhances inflammatory cytokines production but also plays a crucial role in the plasma membrane repair following macrophage co-culture. These findings reveal novel targets for enhancing macrophage-mediated cytotoxicity in cancer, offering additional avenues for therapeutic intervention.
Published in
Exploitable mechanisms of antibody and CAR mediated macrophage cytotoxicity
Liu T, Zhang M, Farsh T et al. · Nature communications 2025 · PMID 40595560 · doi:10.1038/s41467-025-60745-x
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Also filed as BioProject PRJNA1106773 and SRA study SRP505135. Searching any of these in the dataset finder brings you back here.

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