Enhancing anti-tumor immune responses through combination therapies - epigenetic drugs and immune checkpoint inhibitors

Sep 24, 2026

Epigenetic mechanisms alter gene expression and cellular functions without changing DNA sequence, and abnormal epigenomic regulation can drive cancer and other diseases. Tumor immune responses depend on immune-cell involvement and tumor immunogenicity, both of which may shift under epigenetic changes. The review surveys recent research on how epigenomic alterations in immune cells shape behavior, function, and cancer-cell immunogenicity, emphasizing combined epigenetic medications with immune checkpoint inhibitors targeting PD-1, CTLA-4, TIM-3, and LAG-3.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Epigenetic modifications and cancer

Epigenetic therapies and immune evasion

TYPE Review PUBLISHED 23 November 2023 DOI 10.3389/fimmu.2023.1308264 OPEN ACCESS EDITED BY Mohd Wajid Ali Khan, University of Hail, Saudi Arabia REVIEWED BY Shafeeq Ahmed Mohammed, University Hospital Zürich, Switzerland Raman Parkesh, Council of Scientiﬁc and Industrial Research (CSIR), India *CORRESPONDENCE Yun Shi [yunshi@coh.org](yunshi@coh.org)[ ](yunshi@coh.org)Minggao Zhao [minggao@fmmu.edu.cn](minggao@fmmu.edu.cn)[ ](minggao@fmmu.edu.cn)Dongen Ju [dn19951119@163.com](dn19951119@163.com) †These authors have contributed equally to this work RECEIVED 06 October 2023 ACCEPTED 06 November 2023 PUBLISHED 23 November 2023 CITATION Liang Y, Wang L, Ma P, Ju D, Zhao Mand Shi Y (2023) Enhancing anti-tumor immune responses through combination therapies: epigenetic drugs and immune checkpoint inhibitors. Front. Immunol. 14:1308264 . doi: 10.3389/fimmu.2023.1308264 COPYRIGHT © 2023 Liang, Wang, Ma, Ju, Zhao and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Enhancing anti-tumor immune responses through combination therapies: epigenetic drugs and immune checkpoint inhibitors Ying Liang 1†, Lingling Wang 2†, Peijun Ma 3, Dongen Ju 4*, Minggao Zhao 1* and Yun Shi 5* 1 Precision Pharmacy and Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China, 2Wuchang Hospital Afﬁliated to Wuhan University of Science and Technology, Wuhan Wuchang Hospital, Wuhan, China, 3Clinical Laboratory, Shanghai Mental Health Center, Shanghai, China, 4 Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China, 5 Department of Immunology and Theranostics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute of the City of Hope, Duarte, CA, United States Epigenetic mechanisms are processes that affect gene expression and cellular functions without involving changes in the DNA sequence. This abnormal or unstable expression of genes regulated by epigenetics can trigger cancer and other various diseases. The immune cells involved in anti-tumor responses and the immunogenicity of tumors may also be affected by epigenomic changes. This holds signiﬁcant implications for the development and application of cancer immunotherapy, epigenetic therapy, and their combined treatments in the ﬁght against cancer. We provide an overview of recent research literature focusing on how epigenomic changes in immune cells inﬂuence immune cell behavior and function, as well as the immunogenicity of cancer cells. And the combined utilization of epigenetic medications with immune checkpoint inhibitors that focus on immune checkpoint molecules [e.g., Programmed Death 1 (PD-1), Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4), T cell Immunoglobulin and Mucin Domain (TIM-3), Lymphocyte Activation Gene-3 (LAG-3)] present in immune cells and stromal cells associated with tumors. We highlight the potential of small-molecule inhibitors targeting epigenetic regulators to amplify anti-tumor immune responses . Moreover, we discuss how to leverage the intricate relationship between cancer epigenetics and cancer immunology to create treatment regimens that integrate epigenetic therapies with immunotherapies. KEYWORDS epigenetic regulations, immune cells, T cells, anti-tumor immunity, immune checkpoint inhibitors Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) Introduction Epigenetic modiﬁcations are heritable and alters gene expression by changing chromatin structure and modiﬁcations

FAQs

What are epigenetic mechanisms in the context of cancer?

Epigenetic mechanisms affect gene expression and cellular functions without altering the DNA sequence, including DNA methylation, histone modifications, and non-coding RNA regulation. Such changes can contribute to tumor development and disease states.

How can epigenetic changes influence anti-tumor immunity?

Epigenomic alterations can affect immune-cell behavior and function and may modify tumor immunogenicity. The review highlights how these processes can contribute to immune evasion or enhance immunotherapy potential.

Which immune checkpoint inhibitors are discussed as combination options?

The document focuses on checkpoint molecules present in immune and tumor-associated stromal cells, including PD-1, CTLA-4, TIM-3, and LAG-3, as targets for combined epigenetic and immunotherapeutic regimens.

Sep 24, 2026

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