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Targeting the epigenome to reinvigorate T cells for cancer immunotherapy

Dian Xiong1, Lu Zhang2, Zhi-Jun Sun3,4

  • 1State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430079, China.

Military Medical Research
|December 3, 2023
PubMed

Cancer immunotherapy using immune-checkpoint inhibitors (ICIs) has revolutionized the field of cancer treatment; however, ICI efficacy is constrained by progressive dysfunction of CD8+ tumor-infiltrating lymphocytes (TILs), which is termed T cell exhaustion. This process is driven by diverse extrinsic factors across heterogeneous tumor immune microenvironment (TIME). Simultaneously, tumorigenesis entails robust reshaping of the epigenetic landscape, potentially instigating T cell exhaustion. In this review, we summarize the epigenetic mechanisms governing tumor microenvironmental cues leading to T cell exhaustion, and discuss therapeutic potential of targeting epigenetic regulators for immunotherapies. Finally, we outline conceptual and technical advances in developing potential treatment paradigms involving immunostimulatory agents and epigenetic therapies.

Keywords:
Cancer microbiomeCombination therapyEpigenetic therapyImmune checkpoint blockadeImmune macroenvironmentImmunometabolismSpatial immune contextureT cell exhaustion

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