Neoplasma Vol.70, No.6, p. 713–721, 2023
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| Title: miR-124 delivered by BM-MSCs-derived exosomes targets MCT1 of tumor-infiltrating Treg cells and improves ovarian cancer immunotherapy |
| Author: Tian Gao, Yong-Qing Lin, Hai-Yan Ye, Wu-Mei Lin |
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Abstract: 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 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 the 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.
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| Keywords: miR-124; BM-MSC; Treg; exosome; monocarboxylate transporter 1 (MCT1) |
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Published online: 15-Nov-2023
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| Year: 2023, Volume: 70, Issue: 6 |
Page From: 713, Page To: 721 |
doi:10.4149/neo_2023_230711N362
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