Exosomes derived from mesenchymal stem cells (MSC-Exo) are effective in modulating immunity. However, the role of MSC-Exo in clear cell renal cell carcinoma (ccRCC) is unclear. Our study was performed to identify if exosomal microRNA (miRNA) can be used as potential noninvasive biomarkers for ccRCC therapy. An orthotopic ccRCC mouse model was established, followed by MSC-Exo injection (1 mL, 20 μg/mL). The metastases of tumors were observed using HE staining, while number of dendritic cells, natural killing (NK) T cells and CD8⁺ T cells was measured using flow cytometry. It was observed that MSC-Exo treatment significantly inhibited metastasis and growth of tumors, and improved immune response in vivo. As for in vitro assay, naive T cells were treated with MSC-Exo, followed by detection of T cell proliferation using EdU staining and CFSE assay. Results also showed that MSC-Exo facilitated sensitivity of ccRCC cells to NK T cells. Our experimental data further showed that miR-182 could be delivered by MSC-Exo in ccRCC, which targeted vascular endothelial growth factor A (VEGFA), as dual-luciferase reporter assays validated. In conclusion, miR-182 contained in MSC-Exo promoted immune response of T cells by suppressing VEGFA expression, thus alleviating ccRCC development.

来自间充质干细胞 (MSC-Exo) 的外泌体可有效调节免疫。然而，MSC-Exo 在透明细胞肾细胞癌 (ccRCC) 中的作用尚不清楚。我们的研究旨在确定外泌体 microRNA (miRNA) 是否可以用作 ccRCC 治疗的潜在非侵入性生物标志物。建立原位ccRCC小鼠模型，然后进行MSC-Exo注射（1 mL，20 μg/mL）。HE染色观察肿瘤的转移情况，流式细胞仪检测树突状细胞、自然杀伤（NK）T细胞和CD8 ^{+ T细胞的数量。}观察到MSC-Exo治疗显着抑制了肿瘤的转移和生长，并改善了体内免疫反应。至于体外试验，用 MSC-Exo 处理幼稚 T 细胞，然后使用 EdU 染色和 CFSE 试验检测 T 细胞增殖。结果还表明，MSC-Exo 促进了 ccRCC 细胞对 NK T 细胞的敏感性。我们的实验数据进一步表明 miR-182 可以通过 MSC-Exo 在 ccRCC 中递送，其靶向血管内皮生长因子 A (VEGFA)，正如双荧光素酶报告基因测定所验证的那样。总之，MSC-Exo 中含有的 miR-182 通过抑制 VEGFA 的表达来促进 T 细胞的免疫反应，从而减轻 ccRCC 的发展。