肿瘤微环境中肿瘤相关巨噬细胞的代谢重编程研究进展

肿瘤相关巨噬细胞(TAMs)是肿瘤微环境中的重要组成部分,在多种实体瘤中占据肿瘤体积的一半以上,具有高度的可塑性和异质性。在肿瘤发展的早期阶段,TAMs通过其吞噬和抗氧化功能介导抗肿瘤作用。然而,恶性肿瘤细胞为了满足自我更新和增殖的需要,不断调整其代谢模式,导致肿瘤微环境(TME)中的乳酸盐、活性氧、一氧化氮、花生四烯酸和前列腺素等代谢物累积增加,引起炎症微环境改变,从而改变TAMs的代谢和功能,最终促进肿瘤发展。因此,研究TME中TAMs的代谢变化对认识肿瘤的发生发展过程和临床治疗具有重要意义。该文旨在探讨肿瘤进展过程中TAMs在TME内的代谢及免疫反应变化以及如何以此作为靶标开展治疗,以期阐明TAMs代谢与TME的免疫反应之间的密切联系,揭示由TAMs的代谢产生肿瘤免疫抑制的机制,为肿瘤免疫疗法提供新的治疗思路和途径。

Progress in Metabolic Reprogramming of Tumor-associated Macrophages in Tumor Microenvironment

Occupying more than half of the tumor volume in a variety of solid tumors, tumor-associated macrophages (TAMs) are an important part of the tumor microenvironment (TME) with high plasticity and heterogeneity. In the early stages of tumor development, TAMs mediate antitumor effect through phagocytosis and their antioxidant functions. However, in order to meet the needs of self-renewal and proliferation, malignant tumor cells continuously adjust their metabolic patterns, leading to the accumulation of metabolites such as lactate, reactive oxygen species, nitric oxide, arachidonic acid and prostaglandin in the TME, which results in the changes in its inflammatory profiles, thereby altering the metabolism and function of TAMs and ultimately promoting the tumor development. Therefore, further understanding of the metabolism and immune responses of TAMs in the TME during tumor progression is warranted and the investigation may lead to identification of novel potential targets for cancer immunotherapy. This review aims to clarify the close relationship between TAMs metabolism and TME immune response, to reveal the mechanism of tumor immunosuppression produced by TAMs metabolism, and to provide new treatment ideas and approaches for tumor immunotherapy.