GEO series

BACH2 regulates T cell lineage states to enhance CAR T cell function [Cut & Run]

GSE312367 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 9 samples Submitted 2025/12/08 Platform GPL34284

Summary

Nearly all chimeric antigen receptors (CARs) signal in the absence of antigen, referred to as “tonic signaling”. Tonic signaling of CARs containing the CD28 costimulatory domain has been shown to driveT cell exhaustion; in contrast, we found that tonic signaling of 41BB-containing CARs enhances T cell function. Using a panel of CARs targeting CD22, we identified that tonic 41BB signaling activatesBACH2, a transcriptional regulator that directs stem and memory programs. Overexpression of BACH2 prevented tonic CD28-driven exhaustion but locked CAR T cells in quiescent states. To overcome this, we linked BACH2 to a degradation domain and found that tuning BACH2 expression enhanced long-term efficacy of exhaustion-prone CAR T cells targeting liquid and solid tumors. Through interrogation of CAR products, we also found an association between BACH2 activity and clinical outcomes in patients with leukemia. These data identify a central role for BACH2 in regulating CAR T cell efficacy.

Published in

BACH2 regulates T cell lineage state to enhance CAR T cell function

Chang TC, Heard A, Lattin J et al. · Nature immunology 2026 · PMID 41545540 · doi:10.1038/s41590-025-02391-5

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Direct links to NCBI, no account and no request form: the whole study as GSE312367_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 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 PRJNA1373179 and SRA study SRP651062. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41545540) ↗

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