Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
EBioMedicine. 2021 Nov;73:103627. doi: 10.1016/j.ebiom.2021.103627. Epub 2021 Oct 14.
Disordered metabolic states, which are characterised by hypoxia and elevated levels of metabolites, particularly lactate, contribute to the immunosuppression in the tumour microenvironment (TME). Excessive lactate secreted by metabolism-reprogrammed cancer cells regulates immune responses via causing extracellular acidification, acting as an energy source by shuttling between different cell populations, and inhibiting the mechanistic (previously 'mammalian') target of rapamycin (mTOR) pathway in immune cells. This review focuses on recent advances in the regulation of immune responses by lactate, as well as therapeutic strategies targeting lactate anabolism and transport in the TME, such as those involving glycolytic enzymes and monocarboxylate transporter inhibitors. Considering the multifaceted roles of lactate in cancer metabolism, a comprehensive understanding of how lactate and lactate-targeting therapies regulate immune responses in the TME will provide insights into the complex relationships between metabolism and antitumour immunity.
代谢紊乱状态的特点是缺氧和代谢物水平升高,特别是乳酸,这有助于肿瘤微环境(TME)中的免疫抑制。代谢重编程的癌细胞过度分泌的乳酸通过引起细胞外酸化、在不同细胞群之间穿梭作为能量源、以及抑制免疫细胞中的机械(先前的“哺乳动物”)雷帕霉素(mTOR)途径来调节免疫反应。本综述重点介绍了乳酸对免疫反应的调节的最新进展,以及针对 TME 中乳酸合成和转运的治疗策略,例如涉及糖酵解酶和单羧酸转运体抑制剂的策略。考虑到乳酸在癌症代谢中的多方面作用,全面了解乳酸和乳酸靶向治疗如何调节 TME 中的免疫反应将深入了解代谢与抗肿瘤免疫之间的复杂关系。
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