Abstract
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.
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Acknowledgements
The authors would like to thank Mrs. Zhuoqi Liu and Mrs. Xiaohong Yang for their insightful comments during their review of this manuscript.
Funding
This work was supported by National Natural Science Foundation of China (81560464 and 31960152 to D.L.), Applied Research and Cultivation Program of Jiangxi Provincial Department of Science and Technology (20212BAG70036 to S.Z.) and Jiangxi Provincial Education Department foundation Project (GJJ218911 to S.Z.).
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CW contributed to Conceptualization, Methodology, Software, Validation, Visualization, Formal analysis, Investigation, Data Curation, Writing-Original Draft; LX contributed to Methodology; Validation; Resources; Writing-Review and Editing; WZ contributed to Methodology; Validation; Resources; LL: Validation; Resources; SZ contributed to Conceptualization, Writing-Review and Editing; DL contributed to Conceptualization, Resources, Writing-Review and Editing, Supervision.
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Wang, C., Xue, L., Zhu, W. et al. Lactate from glycolysis regulates inflammatory macrophage polarization in breast cancer. Cancer Immunol Immunother 72, 1917–1932 (2023). https://doi.org/10.1007/s00262-023-03382-x
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DOI: https://doi.org/10.1007/s00262-023-03382-x