The role of m6A-mediated PD-1/PD-L1 in antitumor immunity

Li Liu; Long Liang; Hui Li; Wenjun Shao; Chaoying Yang; Feng Lin; Jing Liu; Ji Zhang

doi:10.1016/j.bcp.2023.115460

The role of m6A-mediated PD-1/PD-L1 in antitumor immunity

Biochem Pharmacol. 2023 Apr:210:115460. doi: 10.1016/j.bcp.2023.115460. Epub 2023 Feb 21.

Authors

Li Liu¹, Long Liang², Hui Li³, Wenjun Shao¹, Chaoying Yang², Feng Lin⁴, Jing Liu⁵, Ji Zhang⁶

Affiliations

¹ The First Affiliated Hospital, Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hengyang Medical School, University of South China, Hengyang, 421001 Hunan, China.
² Hunan Province Key Laboratory of Basic and Applied Hematology, Molecular Biology Research Center & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078 Hunan, China.
³ Hunan Province Key Laboratory of Basic and Applied Hematology, Molecular Biology Research Center & Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078 Hunan, China; Department of Dermatology, Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Clinical Research Center for Cancer Immunotherapy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
⁴ Department of Urology Surgery, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, 518033 Guangdong, China. Electronic address: lf0237@gzucm.edu.cn.
⁵ Department of Dermatology, Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Clinical Research Center for Cancer Immunotherapy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: jingliucsu@hotmail.com.
⁶ The First Affiliated Hospital, Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, Hengyang Medical School, University of South China, Hengyang, 421001 Hunan, China; The Affiliated Nanhua Hospital, Department of Clinical Laboratory, Hengyang Medical School, University of South China, Hengyang, 421002 Hunan, China. Electronic address: jizhang@fsyy.usc.edu.cn.

PMID: 36822438
DOI: 10.1016/j.bcp.2023.115460

Abstract

N6-methyladenosine (m6A) is the most prevalent, abundant and conserved type of internal posttranscriptional RNA modification in eukaryotic cells. Emerging evidence suggests that m6A modifications perform important functions that affect antitumor immunity. Programmed death 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) are the two most well-studied immune checkpoint pathways. The interaction of PD-L1 with its receptor PD-1 inhibits cytotoxic T-cell-mediated tumor responses, and blockade of this interaction has proven to be an effective immunotherapy strategy in various cancers. Unfortunately, few cancer patients benefit from the two tools due to uncertain resistance. m6A plays an important role in affecting RNA biogenesis and process in various cancers. Understanding the molecular mechanism of drug resistance will promote the development of personalized clinical management. In this review, we systematically discussed the mechanisms by which m6A regulates PD-1 and PD-L1 expression and further their functions in the process of tumor immunotherapy and the potential application prospects of m6A-associated molecules. Moreover, mounting m6Ascore is established to evaluate the prognosis of cancer.

Keywords: Cancer; Immunotherapy; N6-methyladenosine; PD-1; PD-L1.

Publication types

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

MeSH terms

Adenosine
B7-H1 Antigen*
Humans
Immunotherapy
Programmed Cell Death 1 Receptor*
RNA

Substances

B7-H1 Antigen
Programmed Cell Death 1 Receptor
Adenosine
RNA