Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review)

The excessive buildup of lactic acid within the tumor microenvironment (TME) serves as a hallmark of metabolic reprogramming in cancer. New studies have revealed that lactic acid is an energy metabolic product and a core biological signal that regulates the malignant process of tumors. It plays multiple roles in metabolic reprogramming, protein lactate modification, immune escape, drug resistance generation, epigenetic regulation and metastatic spread. It also has significant negative implications for patient survival. In this review, the advances in understanding the metabolic mechanisms of lactate in the TME and its crosstalk with various of immune cells were systematically reviewed and its therapeutic potential in the following ways was explored: Targeting lactate synthesis (e.g., lactate dehydrogenase inhibitors); interfering with lactate catabolism (e.g., monocarboxylate transporter blockers); and regulating lactate shuttling (microenvironmental cell-to-cell communication). The review aimed to identify new targets and ideas for anticancer strategies by analyzing the lactate metabolic network.