Karimova Adelya F, Khalitova Adelya R, Suezov Roman, Markov Nikita, Mukhamedshina Yana, Rizvanov Albert A, Huber Magdalena, Simon Hans-Uwe, Brichkina Anna
Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
Institute of Systems Immunology, Center for Tumor and Immune Biology, Philipps University of Marburg, Marburg, Germany.
Eur J Cancer. 2025 May 2;220:115332. doi: 10.1016/j.ejca.2025.115332. Epub 2025 Feb 28.
Tumor-associated macrophages (TAMs) play a pivotal role in the tumor microenvironment (TME), actively contributing to the formation of an immunosuppressive niche that fosters tumor progression. Consequently, there has been a growing interest in targeting TAMs as a promising avenue for cancer therapy. Recent advances in the field of immunometabolism have shed light on the influence of metabolic adaptations on macrophage physiology in the context of cancer. Here, we discuss the key metabolic pathways that shape the phenotypic diversity of macrophages. We place special emphasis on how metabolic reprogramming impacts the activation status of TAMs and their functions within the TME. Additionally, we explore alterations in TAM metabolism and their effects on phagocytosis, production of cytokines/chemokines and interaction with cytotoxic T and NK immune cells. Moreover, we examine the application of nanomedical approaches to target TAMs and assess the clinical significance of modulating the metabolism of TAMs as a strategy to develop new anti-cancer therapies. Taken together, in this comprehensive review article focusing on TAMs, we provide invaluable insights for the development of effective immunotherapeutic strategies and the enhancement of clinical outcomes for cancer patients.
肿瘤相关巨噬细胞（TAMs）在肿瘤微环境（TME）中发挥着关键作用，积极促进免疫抑制微环境的形成，从而推动肿瘤进展。因此，将TAMs作为一种有前景的癌症治疗途径的关注度日益增加。免疫代谢领域的最新进展揭示了在癌症背景下代谢适应对巨噬细胞生理学的影响。在此，我们讨论塑造巨噬细胞表型多样性的关键代谢途径。我们特别强调代谢重编程如何影响TAMs的激活状态及其在TME中的功能。此外，我们探讨TAM代谢的改变及其对吞噬作用、细胞因子/趋化因子产生以及与细胞毒性T细胞和NK免疫细胞相互作用的影响。此外，我们研究纳米医学方法靶向TAMs的应用，并评估调节TAMs代谢作为开发新抗癌疗法策略的临床意义。总之，在这篇聚焦TAMs的综合综述文章中，我们为开发有效的免疫治疗策略和改善癌症患者的临床结局提供了宝贵的见解。
