Exosomal miR-125b-5p derived from mesenchymal stromal/stem cell enhances anti-PD-1 therapy in mouse colon cancer model

作者：Mengmeng Jiang, Jia Liu, Shengquan Hu, Xueqin Yan, Yongkai Cao, Zhengzhi Wu · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04227-3 · 被引用次数：10 · 研究领域：Extracellular vesicles in disease、Cancer Immunotherapy and Biomarkers、MicroRNA in disease regulation

Abstract Background There is compelling evidence that FoxP3 + regulatory T cells (Tregs) play a critical role in promoting tumor immune evasion. Our prior research demonstrated that the expression of miR-125b-5p directly inhibits Tregs by targeting TNFR2 and FoxP3. Given the significant therapeutic potential of mesenchymal stromal/stem cell (MSC)-derived exosomes (MSC-EXO) in cancer treatment, the potential role of MSC-EXO in augmenting anti-tumor immunotherapy through the delivery of miR-125b-5p remains unexplored. Methods Nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were employed to characterize exosomes derived from MSCs. Flow cytometry analysis was conducted to investigate the function of exosomal miR-125b-5p both in vitro and in vivo. Mouse MC38 tumor models were administrated MSC-derived exosomes containing miR-125b-5p via tail vein injection, with or without the concurrent injection (intraperitoneally, i.p.) of anti-PD-1 antibodies. Results Our results indicated that exosomal miR-125b-5p derived from MSC significantly inhibited the expansion, proliferation and suppressive function of Tregs in vitro. Moreover, we observed a marked reduction in tumor growth in mice treated with exosomal miR-125b-5p. Notably, while anti-PD-1 therapy alone achieved a cure rate of approximately 30% in a mouse model of colon cancer, the combined administration of exosomal miR-125b-5p significantly enhanced the therapeutic efficacy, resulting in a more than ...