GEO series

Targeting the ADAR1 p150 isoform triggers tumor growth inhibition and antitumor immunity to overcome immunotherapy resistance

GSE316054 Mus musculus; Homo sapiens Expression profiling by high throughput sequencing 52 samples Submitted 2026/04/12 Platform GPL24676Platform GPL24247

Summary

Cancer immunotherapy efficacy is often limited by primary and acquired resistance. The RNA- editing enzyme ADAR1 has emerged as a key regulator of tumor immune evasion, yet therapeutic targeting is challenged by the essential physiological roles of its constitutively expressed p110 isoform. Here, we identify the interferon-inducible p150 isoform and its Zα domain as a critical therapeutic vulnerability. We demonstrate that ADAR1 p150 is frequently overexpressed in human cancers and correlates with an immunosuppressive tumor microenvironment. Genetic ablation of ADAR1 p150 intrinsically inhibits tumor proliferation and extrinsically triggers a robust type I interferon response and profound remodeling of the tumor immune landscape, converting immunologically "cold" tumors to "hot." Furthermore, we establish that myeloid-specific ADAR1 deletion synergizes with anti-PD-1 therapy by enhancing antigen presentation and fostering a pro-inflammatory microenvironment. Crucially, we delineate the Zα domain as the essential structural determinant for dsRNA editing selectivity. Targeted disruption of this domain alone, without affecting the catalytic deaminase domain, is sufficient to recapitulate the potent antitumor effects of complete ADAR1 ablation, leading to accumulation of immunogenic dsRNA, activation of cytosolic sensors (MDA5/PKR), and potent anti-tumor immunity. Our work provides a compelling rationale for selectively targeting the ADAR1 p150-Zα axis to reverse malignant RNA editing and overcome resistance to immunotherapy, offering a refined strategy with a potentially superior therapeutic index.

Published in

Targeting ADAR1 p150 triggers tumor inhibition and antitumor immunity to overcome immunotherapy resistance

Ai ZE, Bian Y, Li G et al. · iScience 2026 · PMID 42221825 · doi:10.1016/j.isci.2026.115978

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Direct links to NCBI, no account and no request form: the whole study as GSE316054_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 52 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1400535 and SRA study SRP661019. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42221825) ↗

Study design

20 conditions, mostly in duplicate

HGC27-788-Adar-N173S-21-IFNB ×2 HGC27-788-Adar-N173S-21-PBS ×2 HGC27-788-IFNB ×2 HGC27-788-PBS ×2 OE21-788-Adar-N173S-2-IFNB ×2 OE21-788-Adar-N173S-2-PBS ×2 OE21-788-IFNB ×2 OE21-788-PBS ×2 +12 more

Supports a between-group comparison across 40 samples.

20 replicated groups read from the first 40 of 52 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.

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