Lactate from glycolysis regulates inflammatory macrophage polarization in breast cancer

Globally, breast cancer is one of the leading causes of cancer death in women. Metabolic reprogramming and immune escape are two important mechanisms supporting the progression of breast cancer. Lactate in tumors mainly comes from glycolysis and glutaminolysis. Using multiomics data analysis, we found that lactate is mainly derived from glycolysis in breast cancer. Single-cell transcriptome analysis found that breast cancer cells with higher malignancy, especially those in the cell cycle, have higher expression levels of glycolytic metabolic enzymes. Combined with clinical data analysis, it was found that the expression of the lactate transporter SLC16A3 is correlated with breast cancer molecular subtypes and immune infiltration. Among 22 immune cells, macrophages are the most abundant immune cells in breast cancer tissues, and the proportion of M1 macrophages is lower in the high SLC16A3 expression group. Finally, in vitro experiments confirmed that lactate could inhibit the expression of M1 macrophage markers at both RNA and protein levels. In conclusion, we found that lactate produced by glycolysis regulates the polarization of inflammatory macrophages in breast cancer.

Automated summary

Globally, breast cancer is a leading cause of cancer death in women. Metabolic reprogramming and immune escape play important roles in breast cancer progression. Lactate in tumors is mainly derived from glycolysis. Through multiomics data analysis, it was found that breast cancer cells with higher malignancy and in the cell cycle have higher expression of glycolytic metabolic enzymes. Clinical data analysis showed that the lactate transporter SLC16A3 is correlated with breast cancer molecular subtypes and immune infiltration. Macrophages are the most abundant immune cells in breast cancer tissues, and the high expression group of SLC16A3 has a lower proportion of M1 macrophages. In vitro experiments confirmed that lactate could inhibit the expression of M1 macrophage markers at both RNA and protein levels. In conclusion, lactate produced by glycolysis regulates the polarization of inflammatory macrophages in breast cancer.