CRISPR screens uncover Dusp5 and Zfp219 as drivers of age-related T cell dysfunction
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A study published in Cell on October 18, 2026 used single-cell CRISPR screens to identify two genes, Dusp5 and Zfp219, that drive CD8+ T cell dysfunction in tumors of aged mice. Deleting Zfp219 triggered epigenetic reprogramming and increased expression of cytotoxic molecules, and when combined with immune checkpoint inhibitors it cleared tumors in aged mice. In humans, higher ZNF219 levels in intratumoral CD8+ T cells correlated with worse survival after immunotherapy in older patients, suggesting the finding translates across species. The work names two targetable genes for rejuvenating antitumor immunity in aging. Open questions include how to turn Zfp219/ZNF219 inhibition into a therapy and how it would be tested in older cancer patients.
Written by a model from the reports · updated 3 hours ago
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- CellPickCRISPR screens identify targets to rescue age-related T cell dysfunction in cancer.
Single-cell CRISPR screens identified Dusp5 and Zfp219 as drivers of CD8+ T cell dysfunction in aged tumors. Deleting Zfp219 caused epigenetic reprogramming, raised cytotoxic molecule expression, and combined with immune checkpoint inhibitors to clear tumors in aged mice; human ZNF219 levels in intratumoral CD8+ T cells correlated with worse survival after immunotherapy in older patients. The work names two targetable genes for rejuvenating antitumor immunity in aging.
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