摘要
肿瘤代谢重编程与免疫逃逸协同促进肿瘤进展,其中甲硫氨酸(methionine,Met)代谢通过表观遗传调控和免疫微环境重塑发挥关键作用。本文系统总结了Met代谢异常导致肿瘤细胞“甲硫氨酸成瘾”及维持恶性表型的机制,并阐述其对免疫系统的多重调控:诱导T细胞耗竭、促进M2型巨噬细胞极化、抑制NK细胞活性及增强肿瘤相关成纤维细胞功能。同时,探讨靶向Met代谢治疗策略,包括甲硫氨酸限制性饮食、代谢酶(MAT2A、NNMT)抑制剂及表观遗传靶点(PRMT5抑制剂),为开发Met靶向疗法提供理论参考。
Tumor metabolic reprogramming and immune escape synergistically promote tumor progression,in which methionine(Met)metabolism plays a key role through epigenetic regulation and immune microenvironment remodelling.This paper systematically summarzes the mechanisms by which aberrant Met metabolism leads to“methionine addiction”and maintains the malignant phenotype of tumor cells,and describes its multiple modulations of the immune system:inducing T-cell depletion,promoting the polarization of M2-type macrophages,inhibiting the activity of NK cells,and enhancing the function of tumor-associated fibroblasts.Furthermore,therapeutic strategies targeting Met metabolism,including methionine-restricted diets,metabolic enzyme(MAT2A,NNMT)inhibitors,and epigenetic targets(PRMT5 inhibitors),are explored to provide theoretical reference for the development of Met-targeted therapies.
作者
黄瑶
陈真
吴红茜
HUANG Yao;CHEN Zhen;WU Hongxi(School of Pharmacy,China Pharmaceutical University,Nanjing 211198,China)
出处
《中国药科大学学报》
北大核心
2025年第3期280-286,共7页
Journal of China Pharmaceutical University
基金
国家自然科学基金项目(No.82273968)。
关键词
甲硫氨酸代谢
T细胞耗竭
肿瘤细胞
代谢-免疫微环境
甲硫氨酸限制饮食
methionine metabolism
T cell depletion
tumor cells
metabolic-immune microenvironment
metabolic therapy with methionine
