The history of research on lactate is quite interesting. At first, it was considered an unnecessary product of glycolysis, which humans use only by converting it back into glucose (gluconeogenesis, Cori cycle). Then it turned out that it is a ready-made source of food for cells and, moreover, that some cells (neurons) may prefer it to glucose. Lactate receptors were discovered, and it became a regulator. Finally, in 2019 (after more than 200 years of study), the lactylation of histones and other proteins ( hundreds of targets) was discovered. Lactate became an epigenetic regulator. A single, very small molecule combines many functions. One of the main functions of interest to oncologists is that lactate, together with hypoxia, is a sign of supply dysfunction in the body and causes reactions aimed at normalization (angiogenesis, etc.). As a result, tumors, with the immune system silent, undergo “normalization,” with blood vessels growing in them to reduce hypoxia and the lactate concentration. In addition, in the tumor microenvironment, where the concentration of lactate is dozens of times higher than normal, lactate acts as an immunosuppressant. In recent years, antitumor therapy has been reoriented from targeting tumor cells themselves to targeting immune cells (using “checkpoints”). Lactate has become one of the targets of such therapy. Various aspects of the molecular biology of lactate are covered in this review. Particular attention is paid to the role of lactate in antitumor therapy.
Vishnyakova et al. (Mon,) studied this question.