Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Medical Oncology, CHA University School of Medicine, Seongnam, Republic of Korea.
Department of Surgery, University of Michigan School of Medicine, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Medical Oncology, CHA University School of Medicine, Seongnam, Republic of Korea.
Curr Opin Immunol. 2024 Dec;91:102491. doi: 10.1016/j.coi.2024.102491. Epub 2024 Oct 4.
Tumor-associated macrophages (TAMs) constitute the primary subset of immune cells within the tumor microenvironment (TME). Exhibiting both phenotypic and functional heterogeneity, TAMs play distinct roles in tumor initiation, progression, and responses to therapy in patients with cancer. In response to various immune and metabolic cues within the TME, TAMs dynamically alter their metabolic profiles to adapt. Changes in glucose, amino acid, and lipid metabolism in TAMs, as well as their interaction with oncometabolites, not only sustain their energy demands but also influence their impact on tumor immune responses. Understanding the molecular mechanisms underlying the metabolic reprogramming of TAMs and their orchestration of metabolic processes can offer insights for the development of novel cancer immunotherapies targeting TAMs. Here, we discuss how metabolism reprograms macrophages in the TME and review clinical trials aiming to normalize metabolic alterations in TAMs and alleviate TAM-mediated immune suppression and protumor activity.
肿瘤相关巨噬细胞（TAMs）构成肿瘤微环境（TME）中主要的免疫细胞亚群。TAMs 表现出表型和功能的异质性，在癌症患者的肿瘤起始、进展和对治疗的反应中发挥着不同的作用。TAMs 会根据 TME 中的各种免疫和代谢线索，动态改变其代谢特征以适应环境。TAMs 中的葡萄糖、氨基酸和脂质代谢的变化，以及它们与致癌代谢物的相互作用，不仅维持了它们的能量需求，还影响了它们对肿瘤免疫反应的影响。了解 TAMs 代谢重编程的分子机制及其代谢过程的协调作用，可以为开发针对 TAMs 的新型癌症免疫疗法提供思路。在这里，我们讨论了代谢如何在 TME 中重塑巨噬细胞，并回顾了旨在使 TAMs 代谢改变正常化和减轻 TAM 介导的免疫抑制和促肿瘤活性的临床试验。
