School of Basic Medical Sciences, Nanchang University, Nanchang, 330006, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang University, Nanchang, 330006, China.
Cancer Immunol Immunother. 2023 Jun;72(6):1917-1932. doi: 10.1007/s00262-023-03382-x. Epub 2023 Feb 2.
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.
在全球范围内，乳腺癌是导致女性癌症死亡的主要原因之一。代谢重编程和免疫逃逸是支持乳腺癌进展的两个重要机制。肿瘤中的乳酸主要来自糖酵解和谷氨酰胺分解。通过多组学数据分析，我们发现乳腺癌中的乳酸主要来自糖酵解。单细胞转录组分析发现，恶性程度较高的乳腺癌细胞，特别是处于细胞周期中的细胞，糖酵解代谢酶的表达水平更高。结合临床数据分析，发现乳酸转运蛋白 SLC16A3 的表达与乳腺癌分子亚型和免疫浸润相关。在 22 种免疫细胞中，巨噬细胞是乳腺癌组织中最丰富的免疫细胞，高 SLC16A3 表达组中 M1 巨噬细胞的比例较低。最后，体外实验证实，乳酸可以在 RNA 和蛋白质水平上抑制 M1 巨噬细胞标志物的表达。总之，我们发现糖酵解产生的乳酸调节乳腺癌中炎症巨噬细胞的极化。
