Lactate and lactylation in tumor immunity.
10.1007/s11684-025-1148-0
- Author:
Liu SONG
1
;
Lingjuan SUN
2
;
Song CHEN
3
;
Peixiang LAN
4
,
5
Author Information
1. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
2. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
3. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. chensong@tjh.tjmu.edu.cn.
4. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. lansong9783@
5. com.
- Publication Type:Review
- Keywords:
TME;
immunosuppressive immune cells;
lactate;
lactylation;
tumor immunity
- MeSH:
Humans;
Neoplasms/metabolism*;
Tumor Microenvironment/immunology*;
Lactic Acid/immunology*;
Warburg Effect, Oncologic;
Animals;
Glycolysis;
Epigenesis, Genetic
- From:
Frontiers of Medicine
2025;19(5):697-720
- CountryChina
- Language:English
-
Abstract:
The Warburg effect, originally discovered by Otto Warburg, refers to the metabolic reprogramming of tumor cells from aerobic oxidation to glycolysis, enabling rapid energy production to support their growth and metastasis. This process is accompanied by the massive production and accumulation of lactate both intracellularly and extracellularly. The resulting acidic microenvironment impairs the normal physiological functions of immune cells and promotes tumor progression. An increasing number of studies indicate that lactate, a key metabolite in the tumor microenvironment (TME), acts as a pivotal immunosuppressive signaling molecule that modulates immune cell function. This review aims to comprehensively examine lactate's role as an immunosuppressive molecule in TME. It focuses on mechanisms such as membrane receptor binding, functional reshaping of immune cells via lactate shuttle transport, epigenetic regulation of gene expression through histone lactylation, and modulation of protein structure and function through nonhistone lactylation, emphasizing lactate's importance in immune regulation within the TME. Ultimately, this review offers novel insights into immunosuppressive therapies aimed at targeting lactate function.
