Research progress on the regulation of tumor malignancy by lactate
10.19401/j.cnki.1007-3639.2025.11.009
- VernacularTitle:乳酸调控肿瘤恶性进程的研究进展
- Author:
Zhiling WANG
1
;
Wanjin CHEN
1
;
Shengtao CHENG
1
Author Information
1. 重庆医科大学感染性疾病分子生物学教育部重点实验室,重庆 400016
- Publication Type:Journal Article
- Keywords:
Lactate;
Tumor;
Lactylation modification;
Metabolic adaptability;
Tumor immunity
- From:
China Oncology
2025;35(11):1067-1075
- CountryChina
- Language:Chinese
-
Abstract:
Malignant tumors represent a major global public health challenge,necessitating urgent innovation in diagnostic and therapeutic strategies.Lactate,a key metabolic product of tumor cell glycolysis,functions not merely as an energy metabolite but also as a signaling molecule to regulate malignant progression.Lactate mediates intercellular metabolite distribution through monocarboxylate transporter(MCT)-driven lactate shuttling and regulates epigenetics via histone lactylation.This integration establishes interconnected networks of energy,amino acid,and lipid metabolism that enhance tumor metabolic plasticity.In immune regulation,lactate induces a shift of T cells toward immunosuppressive phenotypes,impedes CD8+T cell memory differentiation,and attenuates cytotoxicity.Simultaneously,lactate not only reduces the immune efficacy of natural killer(NK)cells but also triggers apoptosis by inducing mitochondrial dysfunction,creating an immune-privileged niche for metastatic sites.Furthermore,elevated lactate levels activate multiple signaling pathways to recruit macrophages and drive their polarization toward the M2 phenotype,fostering an immunosuppressive microenvironment.Current therapeutic strategies target key aspects of lactate metabolism.Inhibiting lactate synthesis reduces lactate accumulation in tumor microenvironment(TME),countering the tumor's metabolic advantage and diminishing its role in driving metabolic reprogramming.Additionally,promoting the decomposition of lactate represents a promising new direction.Novel agents employing bioenzymes or biomimetic catalytic systems enhance local lactate clearance,alleviating the immunosuppressive effects of the acidic TME.This review comprehensively outlined the lactate-mediated regulatory network,aiming to provide systematic research directions and translational insights for developing more effective anti-tumor therapies.
