Department of Molecular and Cellular Biology, Roswell Park Cancer Comprehensive Cancer Center, Buffalo, NY, USA.
FEBS J. 2023 Jun;290(12):3040-3058. doi: 10.1111/febs.16465. Epub 2022 May 7.
Tumour-associated macrophages (TAMs) are highly plastic and are broadly grouped into two major functional states, namely the pro-inflammatory M1-type and the pro-tumoural M2-type. Conversion of the functional states of TAMs is regulated by various cytokines, chemokines growth factors and other secreted factors in the microenvironment. Dysregulated metabolism is a hallmark of cancer. Emerging evidence suggests that metabolism governs the TAM differentiation and functional conversation in support of tumour growth and metastasis. Aside from the altered metabolism reprogramming in TAMs, extracellular metabolites secreted by cancer, stromal and/or other cells within the tumour microenvironment have been found to regulate TAMs through passive competition for metabolite availability and direct regulation via receptor/transporter-mediated signalling reaction. In this review, we focus on the regulatory roles of different metabolites and metabolic pathways in TAM conversion and function. We also discuss if the dysregulated metabolism in TAMs can be exploited for the development of new therapeutic strategies against cancer.
肿瘤相关巨噬细胞（TAMs）具有高度可塑性，广泛分为两种主要功能状态，即促炎型 M1 型和促肿瘤型 M2 型。TAMs 功能状态的转换受微环境中各种细胞因子、趋化因子、生长因子和其他分泌因子的调节。代谢失调是癌症的一个标志。新出现的证据表明，代谢控制着 TAM 的分化和功能转化，以支持肿瘤生长和转移。除了 TAMs 中代谢重编程的改变外，还发现肿瘤微环境中的癌细胞、基质和/或其他细胞分泌的细胞外代谢物通过对代谢物可用性的被动竞争以及通过受体/转运蛋白介导的信号反应的直接调节来调节 TAMs。在这篇综述中，我们重点讨论了不同代谢物和代谢途径在 TAM 转化和功能中的调节作用。我们还讨论了 TAMs 中失调的代谢是否可以被利用来开发针对癌症的新治疗策略。
