Roles and therapeutic implications of m6A modification in cancer immunotherapy

Juan Pan; Tuxiong Huang; Zhenjun Deng; Chang Zou

doi:10.3389/fimmu.2023.1132601

Roles and therapeutic implications of m6A modification in cancer immunotherapy

Front Immunol. 2023 Mar 7:14:1132601. doi: 10.3389/fimmu.2023.1132601. eCollection 2023.

Authors

Juan Pan^{1

2}, Tuxiong Huang³, Zhenjun Deng^{4

5}, Chang Zou^{1

2

6}

Affiliations

¹ National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-targeting Theranostics, Guangxi Medical University, Nanning, Guangxi, China.
² Department of Clinical Medical Research Center, The 2nd Clinical Medical College (Shenzhen People's Hospital) of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
³ Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Pharmacology and International Cancer Center, Shenzhen University Health Science Center, Shenzhen, China.
⁴ Department of Dermatology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.
⁵ The First Affiliated Hospital, Jinan University, Guangzhou, China.
⁶ Shenzhen Public Service Platform On Tumor Precision Medicine and Molecular Diagnosis, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.

Abstract

Recent studies have demonstrated that N6-methyladenosine (m6A), the most abundant, dynamic, and reversible epigenetic RNA modification in eukaryotes, is regulated by a series of enzymes, including methyltransferases (writers), demethylases (erasers), and m6A recognition proteins (readers). Aberrant regulation of m6A modification is pivotal for tumorigenesis, progression, invasion, metastasis, and apoptosis of malignant tumors. Immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, as recognized by the 2018 Nobel Prize in Medicine and Physiology. However, not all cancer patients response to ICI therapy, which is thought to be the result of intricate immune escape mechanisms. Recently, numerous studies have suggested a novel role for m6A epigenetic modification in the regulation of tumor immune evasion. Herein, we review the relevant mechanisms of m6A regulators in regulating various key signaling pathways in cancer biology and how m6A epigenetic modifications regulate the expression of immune checkpoints, opening a new window to understand the roles and mechanisms of m6A epigenetic modifications in regulating tumor immune evasion. In addition, we highlight the prospects and development directions of future combined immunotherapy strategies based on m6A modification targeting, providing directions for promoting the treatment outcomes of immune checkpoint inhibitors.

Keywords: cancer; immune checkpoints; immunotherapy; m6A modification; m6A-regulator inhibitors.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Adenosine
Apoptosis
Carcinogenesis
Humans
Immune Checkpoint Inhibitors* / therapeutic use
Immunotherapy*

Substances

Immune Checkpoint Inhibitors
Adenosine

Grants and funding

This work supported by the Scientific and Technological Innovation Major Base of Guangxi (No.2022-36-Z05), Guangxi Key Research and Development Project (No. AB20117001), Guangxi science and technology bases and talent special project(No. AD17129062), and the grant from Guangdong Basic and Applied Basic Research Foundation (2020B1515120032).