The Regulatory Mechanisms of Lactate: Insights into Metabolic Homeostasis, Immune Modulation, and Tumor Microenvironment

Abstract

Lactate was long regarded as a harmful byproduct of anaerobic respiration, but with recent in-depth research, its multiple key roles in the human body have been revealed. This article systematically reviews the metabolic regulation mechanisms, immune functions of lactate, and its role in cancer. In terms of metabolism, lactate can participate in energy supplementation through lactate shuttles and mitochondrial oxidation, regulate gluconeogenesis, fatty acid metabolism, and cellular redox balance. In cancer cells, lactate is produced in large quantities through aerobic glycolysis to provide energy for their proliferation, and related molecules such as LDH and MCTs may become targets for cancer treatment. In terms of immunity, lactate is not only a marker for disease diagnosis and prognosiscorrelated, but also can bidirectionally regulate inflammatory responses—inhibiting acute inflammation and promoting chronic inflammation. It can also shape the tumour immunosuppressive microenvironment by affecting macrophages, NK cells, etc.  Although breakthroughs have been made in lactate research, issues such as the mechanism of its bidirectional regulation of inflammation and the location of specific reactions remain to be resolved. In the future, research on lactate is expected to provide new directions for the diagnosis and treatment of diseases such as cancer, especially targeting lactate metabolism in the tumor microenvironment to break immunosuppression.