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Epigenetic reprogramming of T cells: unlocking new avenues for cancer immunotherapy

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Abstract

T cells, a key component of cancer immunotherapy, undergo a variety of histone modifications and DNA methylation changes since their bone marrow progenitor stages before developing into CD8+ and CD4+ T cells. These T cell types can be categorized into distinct subtypes based on their functionality and properties, such as cytotoxic T cells (Tc), helper T cells (Th), and regulatory T cells (Treg) as subtypes for CD8+ and CD4+ T cells. Among these, the CD4+ CD25+ Tregs potentially contribute to cancer development and progression by lowering T effector (Teff) cell activity under the influence of the tumor microenvironment (TME). This contributes to the development of therapeutic resistance in patients with cancer. Subsequently, these individuals become resistant to monoclonal antibody therapy as well as clinically established immunotherapies. In this review, we delineate the different epigenetic mechanisms in cancer immune response and its involvement in therapeutic resistance. Furthermore, the possibility of epi-immunotherapeutic methods based on histone deacetylase inhibitors and histone methyltransferase inhibitors are under investigation. In this review we highlight EZH2 as the principal driver of cancer cell immunoediting and an immune escape regulator. We have addressed in detail how understanding T cell epigenetic regulation might bring unique inventive strategies to overcome drug resistance and increase the efficacy of cancer immunotherapy.

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Funding

This work was supported by Basic and Applied Research in Biophysics and Material Science (RSI 4002) by the Department of Atomic Energy (DAE), S. Ramachandran National Bioscience Award for Career Development 2019 (BT/HRD-NBA-NWB/38/2019-20), Department of Biotechnology, and SwarnaJayanti Fellowship (DST/SJF/LSA-02/2017-18), Department of Science and Technology, Govt. of India to C. D.

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Authors and Affiliations

  1. Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata, 700064, India

    Vipin Singh, Sandhik Nandi, Aritra Ghosh, Santanu Adhikary, Shravanti Mukherjee & Chandrima Das

  2. Homi Bhabha National Institute, Mumbai, 400094, India

    Vipin Singh, Sandhik Nandi & Chandrima Das

  3. Indian Institute of Science Education and Research, Kolkata, India

    Aritra Ghosh

  4. Structural Biology & Bio-Informatics Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India

    Santanu Adhikary & Siddhartha Roy

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  1. Vipin Singh
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Contributions

C. D. proposed the review topic. C. D., V. S., S. N., A. G., and S. M. wrote the main manuscript and S. A. and S. R. prepared Figs. 1, 2, and 3. All authors reviewed the manuscript and approved the final version for submission.

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Correspondence to Chandrima Das.

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Singh, V., Nandi, S., Ghosh, A. et al. Epigenetic reprogramming of T cells: unlocking new avenues for cancer immunotherapy. Cancer Metastasis Rev 43, 175–195 (2024). https://doi.org/10.1007/s10555-024-10167-w

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