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Integrated computational analysis identifies therapeutic targets with dual action in cancer cells and T cells

GSE261915 Mus musculus; Homo sapiens Expression profiling by high throughput sequencing 21 samples Submitted 2024/12/25 Platform GPL24676Platform GPL24247
Summary
Many cancer drugs that target cancer cell pathways have detrimental effects on the immune system. We developed a computational platform for the identification of therapeutic targets with beneficial effects in both cancer and immune cells. ICRAFT (https://icraft.pku-genomics.org/) enables integrated analysis of immune-related CRISPR screen datasets, scRNA-Seq data, and pre-treatment RNA-Seq data from clinical trials. This platform enabled the discovery of a substantial number of targets with dual action in cancer cells and T cells. Among these, TNFAIP3, a ubiquitin-editing enzyme also known as A20, emerged as a leading target. Inactivating TNFAIP3 in cancer cells sensitizes them to immune attacks by activating the NF-κB pathway, while targeting it in T cells significantly enhances their antitumor efficacy.
Published in
Integrated computational analysis identifies therapeutic targets with dual action in cancer cells and T cells
Luo C, Zhang R, Guo R et al. · Immunity 2025 · PMID 40023158 · doi:10.1016/j.immuni.2025.02.007
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Direct links to NCBI, no account and no request form: the whole study as GSE261915_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 21 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1089567 and SRA study SRP496423. Searching any of these in the dataset finder brings you back here.

Study design
7 conditions, mostly in triplicate
A549 cancer cell, sgTNFAIP3-1, ×3 A549 cancer cell, sgTNFAIP3-2, ×3 A549 cancer cell, sgCtrl, ×3 OT-1 cell, untreated, sgCtrl, ×3 OT-1 cell, sgCtrl, co-culture with cancer cel… ×3 OT-1 cell, sgTnfaip3-1, co-culture with cance… ×3 OT-1 cell, sgTnfaip3-2, co-culture with cance… ×3

Supports a between-group comparison across 21 samples.

7 replicated groups read from 21 sample titles; they account for 21 of them. Check it against the sample list below before relying on it.

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