Department of Gynecology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
Neoplasma. 2023 Dec;70(6):713-721. doi: 10.4149/neo_2023_230711N362. Epub 2023 Nov 15.
Metabolic rewiring of tumor cells leads to an enrichment of lactate in the tumor microenvironment (TME). This lactate-rich environment of solid tumors has been reported to support tumor-infiltrating regulatory T (Treg) cells. Therefore, agents that modify the lactate metabolism of Treg cells have therapeutic potential. Monocarboxylate transporter 1 (MCT1), which Treg cells predominantly express, plays an essential role in the metabolism of tumor-infiltrating Treg cells. In this study, we show that miR-124 directly targets MCT1 and reduces lactate uptake, eventually impairing the immune-suppressive capacity of Treg cells. Particularly, exosomal miR-124 derived from bone marrow mesenchymal stromal cells (BM-MSCs) slows tumor growth and increases response to PD-1 blockade therapy. These data indicate a potential treatment strategy for improving immune checkpoint blockade therapy using miR-124-carried BM-MSCs-derived exosomes.
肿瘤细胞的代谢重编程导致肿瘤微环境（TME）中乳酸盐的富集。已报道这种富含乳酸盐的实体瘤环境支持肿瘤浸润调节性 T（Treg）细胞。因此，能够修饰 Treg 细胞的乳酸盐代谢的药物具有治疗潜力。单羧酸转运蛋白 1（MCT1），Treg 细胞主要表达该蛋白，在肿瘤浸润 Treg 细胞的代谢中发挥重要作用。在这项研究中，我们表明 miR-124 可直接靶向 MCT1 并减少乳酸盐摄取，最终损害 Treg 细胞的免疫抑制能力。特别地，源自骨髓间充质基质细胞（BM-MSCs）的外泌体 miR-124 可减缓肿瘤生长并增加对 PD-1 阻断治疗的反应。这些数据表明，使用携带 miR-124 的 BM-MSCs 衍生的外泌体来改善免疫检查点阻断治疗具有潜在的治疗策略。
