Research identifies epigenetic and transcriptomic regulators of stemlike CD8+ CAR T-cell fate (Klem via Wikimedia Commons)

How stemlike CD8+ chimeric antigen receptor (CAR) T-cell (Ts) differentiation to effector-like CD8+ CAR T cells (Teff) or terminally exhausted CD8+ CAR T cells (Tex) is regulated is not well understood. Through single-cell transcriptomic and epigenomic analyses, Zhu et al. show that each of these three CD8+ CAR T-cell subsets are defined by distinct transcription factors. Changes in chromatin accessibility precede transcriptional changes, priming a cell for regulation by the next set of transcription factors. FOXP1 limits Ts to Teff differentiation, whereas KLF2 promotes Teff differentiation and suppresses Tex differentiation. The data may provide new ways to manipulate CD8+ CAR T-cell differentiation for therapeutic benefit.

Zhu Z, …, Wu T. Nat Immunol 2023 November 27;25:117–28.

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