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肿瘤微环境中的乳酸:从免疫调节到治疗。

Lactate in the tumour microenvironment: From immune modulation to therapy.

机构信息

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.

出版信息

EBioMedicine. 2021 Nov;73:103627. doi: 10.1016/j.ebiom.2021.103627. Epub 2021 Oct 14.


DOI:10.1016/j.ebiom.2021.103627
PMID:34656878
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8524104/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf6e/8524104/55e6c37194c5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf6e/8524104/90487e3513ea/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf6e/8524104/41ebfb941e64/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf6e/8524104/55e6c37194c5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf6e/8524104/90487e3513ea/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf6e/8524104/41ebfb941e64/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf6e/8524104/55e6c37194c5/gr3.jpg

相似文献

[1]
Lactate in the tumour microenvironment: From immune modulation to therapy.

EBioMedicine. 2021-11

[2]
The Immune Consequences of Lactate in the Tumor Microenvironment.

Adv Exp Med Biol. 2020

[3]
The oncogenic and clinical implications of lactate induced immunosuppression in the tumour microenvironment.

Cancer Lett. 2021-3-1

[4]
Targeting the Warburg Effect in Cancer: Where Do We Stand?

Int J Mol Sci. 2024-3-8

[5]
Lactate and Lactate Transporters as Key Players in the Maintenance of the Warburg Effect.

Adv Exp Med Biol. 2020

[6]
Immunometabolic rewiring in tumorigenesis and anti-tumor immunotherapy.

Mol Cancer. 2022-1-21

[7]
Metabolic profiles of regulatory T cells in the tumour microenvironment.

Cancer Immunol Immunother. 2021-9

[8]
Metabolism of Dendritic Cells in Tumor Microenvironment: For Immunotherapy.

Front Immunol. 2021

[9]
Immunometabolism at the Nexus of Cancer Therapeutic Efficacy and Resistance.

Front Immunol. 2021

[10]
The cancer metabolic reprogramming and immune response.

Mol Cancer. 2021-2-5

引用本文的文献

[1]
Metabolic Plasticity and Cancer Stem Cell Metabolism: Exploring the Glycolysis-OXPHOS Switch as a Mechanism for Resistance and Tumorigenesis.

Stem Cell Rev Rep. 2025-8-29

[2]
Therapeutic Strategies Targeting Aerobic Glycolysis in Cancer and Dynamic Monitoring of Associated Metabolites.

Cells. 2025-8-19

[3]
Metabolic Reprogramming Shapes the Progression and Therapeutic Landscape of Ovarian Cancer.

Cancer Manag Res. 2025-8-19

[4]
Exploring the role of ferroptosis in esophageal cancer: mechanisms and therapeutic implications.

Cell Death Discov. 2025-8-25

[5]
FOXK1-induced upregulation of NXPH4 predicts poor prognosis and promotes hepatocellular carcinoma progression via PI3K/Akt pathway.

Am J Cancer Res. 2025-7-15

[6]
Triptolide targets PPP2CA/ITGA5 axis to suppress lactate-driven ovarian cancer progression.

Chin Med. 2025-8-6

[7]
Crizotinib: A Novel Strategy to Reverse Immunosuppression in Melanoma by Targeting Lactate Transport.

MedComm (2020). 2025-7-21

[8]
Lactate and lactylation in breast cancer: current understanding and therapeutic opportunities.

Cancer Biol Med. 2025-7-16

[9]
Lactate and lactylation: emerging roles in autoimmune diseases and metabolic reprogramming.

Front Immunol. 2025-6-27

[10]
Nanomedicine-driven tumor glucose metabolic reprogramming for enhanced cancer immunotherapy.

Acta Pharm Sin B. 2025-6

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