Glucose metabolism reprogramming in tumor-associated macrophages and targeted therapy
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摘要: 肿瘤相关巨噬细胞（tumor-associated macrophages，TAMs）作为肿瘤微环境（tumor microenvironment，TME）中重要的免疫细胞，具有高度异质性及可塑性，在肿瘤细胞分泌的细胞因子刺激下，可发生表型、代谢及功能变化。TAMs代谢改变以糖代谢重编程为主，M1型TAMs有氧糖酵解、磷酸戊糖途径增强，三羧酸循环减弱，具有抗肿瘤功能；M2型TAMs具有完整的三羧酸循环，可促进肿瘤进展。而在TME作用下TAMs具有多种表现形式，其糖代谢重编程可影响肿瘤迁移、侵袭及血管生成，而具体作用机制尚不明确。本文旨在探讨TAMs糖代谢重编程作用机制及其与肿瘤免疫相关性，提示TME中TAMs糖代谢重编程对肿瘤发展和靶向治疗有重要意义，可为肿瘤治疗提供新思路。Abstract: Tumor-associated macrophages (TAMs) are highly heterogeneous and plastic, functioning as critical immune cells in the tumor microenvironment (TME). TAMs change their phenotype, metabolism, and function upon the stimulation of cytokines secreted by tumor cells. Different types of glucose metabolism mainly characterize TAMs metabolism. M1-type TAMs have enhanced aerobic glycolysis and pentose phosphate pathway activity, while triphosphate cycle activity is reduced. In contrast, M2-type TAMs have complete triphosphate cycle activity. The distribution of TAM types within the TME varies, and the reprogramming of glucose metabolism can affect tumor migration, invasion, and angiogenesis. However, the specific mechanisms of glucose metabolism reprogramming affecting the tumor environment remain unclear. This review summarizes the current understanding of glucose metabolism reprogramming mechanisms in TAMs and their correlation with the immune response in the TME. Understanding TAM glucose metabolism reprogramming in tumor development is essential for generating targeted therapies and providing new directions for tumor treatment.
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表 1 靶向TAMs极化的临床试验药物
药物 靶点和机制 肿瘤类型 临床试验编号 分期 PLX3397 CSF1R抑制剂 实体瘤 NCT02452424 Ⅰ、Ⅱ IMC-CS4 CSF1R抑制剂 实体瘤 NCT01346358 Ⅰ FPA008 抗CSF1R抗体 晚期胰腺癌 NCT03336216 Ⅱ MLN1202 抗CCR2单克隆抗体 转移性癌 NCT01015560 Ⅱ CP-870, 893 激动性抗CD40抗体 实体瘤 NCT02157831 Ⅰ APX005M 激动性抗CD40抗体 消化系统肿瘤 NCT03165994 Ⅱ 2DG HK-2抑制剂 实体瘤 NCT00096707 Ⅰ 
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