GoKawiilSt. Jude study finds blocking ZMYND8 protein restores exhausted T cell function
Researchers at St. Jude Children's Research Hospital used CRISPR-Cas9 screening in mouse T cell models to identify ZMYND8 as a regulator of T cell exhaustion. Removing ZMYND8 boosted IL-2 signalling in antigen-specific CD8+ T cells, including those engineered with CAR constructs, helping the cells retain function against tumours in mouse models.
GoKawiil's interpretation of the reporting above, not reported fact.
T cell exhaustion is a major barrier to durable responses in cancer immunotherapies such as CAR-T cell treatments, so identifying a molecular target that reverses this state could inform new combination therapies. Because the findings so far come from mouse models using P14, pmel and CD19 CAR-transgenic systems, further work would be needed to determine whether targeting ZMYND8 translates safely and effectively to human T cell therapies.
- ZMYND8 was identified via CRISPR screening as a suppressor of IL-2 signalling in T cells
- Deleting ZMYND8 in mouse CD8+ T cells reduced markers of T cell exhaustion
- Findings originate from preclinical mouse models, including CAR-T systems, not yet human trials
Source: nature.com — Wang, 2026-09-23
Published there as: “Targeting ZMYND8 unleashes IL-2 signalling to override T cell exhaustion”
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