TAM脂质代谢调控:从细胞内重编程到系统性代谢网络OA
Lipid Metabolism Regulation in TAM:From Cellular Reprogramming to Systemic Metabolic Networks
肿瘤相关巨噬细胞(TAM)通过脂质代谢重编程,成为连接局部微环境与系统代谢的核心枢纽.其通过高效的脂质摄取与脂噬介导的胆固醇重分布,支持肿瘤细胞的膜合成、信号激活与侵袭潜能;同时通过过氧化物酶体增殖物激活受体γ(PPARγ)驱动的免疫检查点上调、营养剥夺与腺苷生成,塑造免疫抑制生态位.系统层面,肿瘤通过激活肝脏固醇调节元件结合蛋白-1c(SREBP-1c)与脂肪组织分解,建立双向脂质动员网络,而TAM在此过程中扮演关键中介的角色.不同组织肿瘤微环境塑造了TAM脂质代谢的器官特异性,提示靶向策略需兼顾组织学背景.未来结合代谢组学标志物、饮食干预与免疫联合疗法,有望实现精准靶向代谢的免疫治疗.
Tumor-associated macrophages(TAMs)have become the core hub connecting the local microenvironment and system metabolism through lipid metabolism reprogramming.By enhancing lipid uptake and lipophagy-mediated cholesterol redistribution,TAMs support tumor cell membrane synthesis,signaling activation,and invasive potential.Immune checkpoints upregulation driven by peroxisome proliferator-activated receptor γ,nutrient deprivation,and adenosine production contribute to the formation of an immunosuppressive niche.At the systemic level,tumors orchestrate a bidirectional,lipid-mobilizing network by activating hepatic sterol regulatory element-binding protein-1c and promoting adipose tissue lipolysis,with TAMs serving as key intermediaries in this process.The organ-specific features of TAM lipid metabolism shaped by distinct tumor microenvironments suggest that therapeutic strategies should consider tissue context.Integrating metabolomic biomarkers,dietary interventions,and combination immunotherapies holds promise for achieving precision metabolic immunotherapy.
李宇轩;李昀徽;任欢
518055 深圳,南方科技大学医学院药理学系518055 深圳,南方科技大学医学院药理学系518055 深圳,南方科技大学医学院药理学系
医药卫生
脂质负载巨噬细胞肿瘤微环境脂质代谢脂质网络靶向治疗协同疗法
Lipid-laden macrophagesTumor microenvironmentLipid metab-olismLipid networkTargeted therapyCombination therapy
《肿瘤防治研究》 2026 (1)
43-49,7
广东省教学质量与教学改革工程建设项目(SJZLGC202313)国家自然科学基金面上项目(81871-993)南方科技大学大学生创新项目(Y25411800) Guangdong Province Teach-ing Quality and Teaching Reform Project(No.SJZLGC202313)General Project of National Natural Science Foundation of China(No.81871993)Southern University of Science and Technology Student Innovation Project(No.Y25411800)
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