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miR-124 delivered by BM-MSCs-derived exosomes targets MCT1 of tumor-infiltrating Treg cells and improves ovarian cancer immunotherapy

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Tian Gao, Yong-Qing Lin,  Hai-Yan Ye,  Wu-Mei Lin

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 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.

Received date: 07/11/2023

Accepted date: 11/06/2023

Ahead of print publish date: 11/15/2023

Issue: 6/2023

Volume: 70

Pages: 713 — 721

Keywords: miR-124, BM-MSC, Treg, exosome, monocarboxylate transporter 1 (MCT1)

DOI: 10.4149/neo_2023_230711N362

Pubmed

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