The YTH domain‐containing protein family: Emerging players in immunomodulation and tumour immunotherapy targets

• Published in: Clinical and translational medicine 2024-08, Vol.14 (8), p.e1784-n/a
• Main Authors: Li, Fenghe, Zeng, Chong, Liu, Jie, Wang, Lei, Yuan, Xiaorui, Yuan, Li, Xia, Xiaomeng, Huang, Wei
• Format: Article
• Language: English
• Subjects: anti‐tumour immunity; Humans; Immunomodulation; immunoregulation; Immunotherapy; Immunotherapy - methods; m6A methylation; Neoplasms - immunology; Neoplasms - therapy; Proteins; Review; RNA Splicing Factors - genetics; RNA Splicing Factors - immunology; RNA-Binding Proteins - genetics; RNA-Binding Proteins - immunology; YTH domain‐containing protein family
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.1784

Background The modification of N6‐methyladenosine (m6A) plays a pivotal role in tumor by altering both innate and adaptive immune systems through various pathways, including the regulation of messenger RNA. The YTH domain protein family, acting as “readers” of m6A modifications, affects RNA splicing, stability, and immunogenicity, thereby playing essential roles in immune regulation and antitumor immunity. Despite their significance, the impact of the YTH domain protein family on tumor initiation and progression, as well as their involvement in tumor immune regulation and therapy, remains underexplored and lacks comprehensive review. Conclusion This review introduces the molecular characteristics of the YTH domain protein family and their physiological and pathological roles in biological behavior, emphasizing their mechanisms in regulating immune responses and antitumor immunity. Additionally, the review discusses the roles of the YTH domain protein family in immune‐related diseases and tumor resistance, highlighting that abnormal expression or dysfunction of YTH proteins is closely linked to tumor resistance. Key points This review provides an in‐depth understanding of the YTH domain protein family in immune regulation and antitumor immunity, suggesting new strategies and directions for immunotherapy of related diseases. These insights not only deepen our comprehension of m6A modifications and YTH protein functions but also pave the way for future research and clinical applications. The YTH domain protein family regulates innate and adaptive immunity through regulating multiple immune cells and plays a role in anti‐tumour immunity. The YTH domain protein family influences the tumour immune microenvironment by targeting YAP and metabolic mechanisms, promoting immune escape and metastasis. The YTH domain protein family is a potential target for immune‐related diseases and tumour immunotherapy.