RNA Modifications in Cancer Immune Therapy: Regulators of Immune Cells and Immune Checkpoints

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 Oct 7

PMID 39372415

Authors

Xiangyu Qin

Huali Liu

Qixuan Zhang

Yuhang Che

Tianyu Lei

Fang Tang

Qinyong Hu

Affiliations

Soon will be listed here.

Abstract

RNA modifications are epigenetic changes that alter the structure and function of RNA molecules, playing a crucial role in the onset, progression, and treatment of cancer. Immune checkpoint inhibitor (ICI) therapies, particularly PD-1 blockade and anti-CTLA-4 treatments, have changed the treatment landscape of virous cancers, showing great potential in the treatment of different cancer patients, but sensitivity to these therapies is limited to certain individuals. This review offers a comprehensive survey of the functions and therapeutic implications of the four principal RNA modifications, particularly highlighting the significance of m6A in the realms of immune cells in tumor and immunotherapy. This review starts by providing a foundational summary of the roles RNA modifications assume within the immune cell community, focusing on T cells, NK cells, macrophages, and dendritic cells. We then discuss how RNA modifications influence the intricate regulatory mechanisms governing immune checkpoint expression, modulation of ICI efficacy, and prediction of ICI treatment outcomes, and review drug therapies targeting genes regulated by RNA modifications. Finally, we explore the role of RNA modifications in gene editing, cancer vaccines, and adoptive T cell therapies, offering valuable insights into the use of RNA modifications in cancer immunotherapy.

References

Chen J, Li K, Chen J, Wang X, Ling R, Cheng M . Aberrant translation regulated by METTL1/WDR4-mediated tRNA N7-methylguanosine modification drives head and neck squamous cell carcinoma progression. Cancer Commun (Lond). 2022; 42(3):223-244. PMC: 8923133. DOI: 10.1002/cac2.12273. View

Wang A, Sun Y, Wang X, Yan Z, Wang D, Zeng L . mA methyltransferase METTL16 mediates immune evasion of colorectal cancer cells via epigenetically regulating PD-L1 expression. Aging (Albany NY). 2023; 15(16):8444-8457. PMC: 10496997. DOI: 10.18632/aging.204980. View

Wang Z, Shang J, Qiu Y, Cheng H, Tao M, Xie E . Suppression of the METTL3-mA-integrin β1 axis by extracellular acidification impairs T cell infiltration and antitumor activity. Cell Rep. 2024; 43(2):113796. DOI: 10.1016/j.celrep.2024.113796. View

Zhao Y, Huang S, Tan X, Long L, He Q, Liang X . N -Methyladenosine-Modified CBX1 Regulates Nasopharyngeal Carcinoma Progression Through Heterochromatin Formation and STAT1 Activation. Adv Sci (Weinh). 2022; 9(36):e2205091. PMC: 9798977. DOI: 10.1002/advs.202205091. View

Li J, Zhang H, Wang H . N-methyladenosine modification in cancer biology: Current status and future perspectives. Comput Struct Biotechnol J. 2022; 20:6578-6585. PMC: 9712505. DOI: 10.1016/j.csbj.2022.11.045. View

Qiu X, Yang S, Wang S, Wu J, Zheng B, Wang K . MA Demethylase ALKBH5 Regulates PD-L1 Expression and Tumor Immunoenvironment in Intrahepatic Cholangiocarcinoma. Cancer Res. 2021; 81(18):4778-4793. DOI: 10.1158/0008-5472.CAN-21-0468. View

Wculek S, Cueto F, Mujal A, Melero I, Krummel M, Sancho D . Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2019; 20(1):7-24. DOI: 10.1038/s41577-019-0210-z. View

Wang W, Dong D, Yu P, Chen T, Gao R, Wei J . Prognostic model based on m6A-associated lncRNAs in esophageal cancer. Front Endocrinol (Lausanne). 2022; 13:947708. PMC: 9468245. DOI: 10.3389/fendo.2022.947708. View

Li L, Yang W, Jia D, Zheng S, Gao Y, Wang G . Establishment of a N1-methyladenosine-related risk signature for breast carcinoma by bioinformatics analysis and experimental validation. Breast Cancer. 2023; 30(4):666-684. PMC: 10284980. DOI: 10.1007/s12282-023-01458-1. View

10.

Garcia-Vilchez R, Anazco-Guenkova A, Dietmann S, Lopez J, Moron-Calvente V, DAmbrosi S . METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer. Mol Cancer. 2023; 22(1):119. PMC: 10386714. DOI: 10.1186/s12943-023-01809-8. View

11.

Zhou H, Meng M, Wang Z, Zhang H, Yang L, Li C . The Role of m5C-Related lncRNAs in Predicting Overall Prognosis and Regulating the Lower Grade Glioma Microenvironment. Front Oncol. 2022; 12:814742. PMC: 8971304. DOI: 10.3389/fonc.2022.814742. View

12.

Zhang J, Gao J, Hu M, Xu S, Cheng C, Zheng W . Integrated investigation of the clinical implications and targeted landscape for RNA methylation modifications in hepatocellular carcinoma. Eur J Med Res. 2023; 28(1):46. PMC: 9881284. DOI: 10.1186/s40001-023-01016-7. View

13.

Regmi P, He Z, Lia T, Paudyal A, Li F . N7-Methylguanosine Genes Related Prognostic Biomarker in Hepatocellular Carcinoma. Front Genet. 2022; 13:918983. PMC: 9207530. DOI: 10.3389/fgene.2022.918983. View

14.

Cai J, Chen Z, Zhang Y, Wang J, Zhang Z, Wu J . CircRHBDD1 augments metabolic rewiring and restricts immunotherapy efficacy via mA modification in hepatocellular carcinoma. Mol Ther Oncolytics. 2022; 24:755-771. PMC: 8908059. DOI: 10.1016/j.omto.2022.02.021. View

15.

Chen J, Song Y, Liang G, Zhang Z, Wen X, Li R . A Novel m7G-Related Gene Signature Predicts the Prognosis of Colon Cancer. Cancers (Basel). 2022; 14(22). PMC: 9688272. DOI: 10.3390/cancers14225527. View

16.

Song Z, Wang X, Chen F, Chen Q, Liu W, Yang X . LncRNA MALAT1 regulates METTL3-mediated PD-L1 expression and immune infiltrates in pancreatic cancer. Front Oncol. 2022; 12:1004212. PMC: 9533337. DOI: 10.3389/fonc.2022.1004212. View

17.

Dong L, Chen C, Zhang Y, Guo P, Wang Z, Li J . The loss of RNA N-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8 T cell dysfunction and tumor growth. Cancer Cell. 2021; 39(7):945-957.e10. DOI: 10.1016/j.ccell.2021.04.016. View

18.

Hodgins J, Khan S, Park M, Auer R, Ardolino M . Killers 2.0: NK cell therapies at the forefront of cancer control. J Clin Invest. 2019; 129(9):3499-3510. PMC: 6715409. DOI: 10.1172/JCI129338. View

19.

Chen A, Zhang V, Zhang Q, Sze K, Tian L, Huang H . Targeting the oncogenic m6A demethylase FTO suppresses tumourigenesis and potentiates immune response in hepatocellular carcinoma. Gut. 2024; 74(1):90-102. PMC: 11672076. DOI: 10.1136/gutjnl-2024-331903. View

20.

Song H, Zhang J, Liu B, Xu J, Cai B, Yang H . Biological roles of RNA mC modification and its implications in Cancer immunotherapy. Biomark Res. 2022; 10(1):15. PMC: 8973801. DOI: 10.1186/s40364-022-00362-8. View