Although Myeloid-derived suppressor cells (MDSCs) have a prominent ability to suppress the immune responses of T lymphocytes and propel tumor immune escape, a lack of profound systemic immunesuppression in tumor-bearing mice and tumor patients. The underlying mechanism of these remains unclear. For this purpose, renal cancer-derived exosomes (RDEs) were first labeled with PKH67 and been observed the internalization by MDSCs. Flow cytometry analysis showed the proportion and activity change of MDSCs in spleen and bone marrow induced by RDEs. Further, western blot experiments were used to verify triggered mechanism of MDSCs by RDEs. Finally, proliferation and cytotoxicity of cytotoxic T lymphocytes (CTLs) co-cultured with MDSCs in vitro and a series of experiments in vivo were performed to demonstrate the specific inhibitory effect of RDEs-induced MDSCs. This study suggested that RDEs crucially contributed to presenting antigenic information, activating and driving specific immunosuppressive effect to MDSCs. HSP70, which is highly expressed in RDEs, initiate this process in a toll like receptor 2 (TLR2)-dependent manner. Importantly, RDEs-induced MDSCs could exert an antigen-specific immunosuppression effect on CTL and specific promote renal tumors-growth and immune escape in consequence. The immunosuppression mediated by MDSCs which is induced by RDEs is antigen-specific. HSP70, which is highly expressed in RDEs, plays a pivotal role in this process. Targeted abrogating the function of MDSCs, or eliminating the expression of HSP70 in exosomes, or blocking the crosstalk between them provides a new direction and theoretical support for future immunotherapy.

中文翻译：

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肾癌衍生的外泌体通过 MDSCs 介导的抗原特异性免疫抑制诱导肿瘤免疫耐受。

尽管髓源性抑制细胞 (MDSCs) 具有突出的抑制 T 淋巴细胞免疫反应和推动肿瘤免疫逃逸的能力，但在荷瘤小鼠和肿瘤患者中缺乏深度的全身免疫抑制。这些的潜在机制尚不清楚。为此，首先用 PKH67 标记肾癌衍生的外泌体 (RDE)，并观察到 ​​MDSC 的内化。流式细胞术分析显示RDEs诱导的脾脏和骨髓中MDSCs的比例和活性变化。此外，蛋白质印迹实验被用来验证 RDEs 触发 MDSCs 的机制。最后，体外与 MDSCs 共培养的细胞毒性 T 淋巴细胞 (CTLs) 的增殖和细胞毒性以及一系列体内实验证明了 RDEs 诱导的 MDSCs 的特异性抑制作用。该研究表明，RDE 对呈递抗原信息、激活和驱动对 MDSC 的特异性免疫抑制作用至关重要。HSP70 在 RDE 中高度表达，以类似收费受体 2 (TLR2) 的方式启动这一过程。重要的是，RDEs 诱导的 MDSCs 可以对 CTL 发挥抗原特异性免疫抑制作用，从而特异性促进肾肿瘤生长和免疫逃逸。由 RDEs 诱导的 MDSCs 介导的免疫抑制是抗原特异性的。在 RDE 中高度表达的 HSP70 在这个过程中起着举足轻重的作用。