Abstract Epigenetic regulation is crucial in directing T-cell differentiation, function, and fate, thereby influencing the success of T-cell-based immunotherapies. This review begins with an overview of the evolution of T-cell immunotherapies in cancer treatment. We then examine key epigenetic regulators—such as DNA methylation, mRNA methylation, and histone methylation—and their roles in shaping T-cell states during infection and tumorigenesis. The contributions of these regulators to T-cell exhaustion and lineage commitment are discussed in the context of immunotherapy efficacy. We highlight recent advances in targeting epigenetic pathways to enhance CAR-T and TCR-based therapies and conclude with current challenges and emerging strategies to improve the durability and effectiveness of adoptive T-cell therapies.
Wyce et al. (2026) studied this question.