Collaborative research is reviewed in which mass spectrometry-based proteomics and next generation sequencing were used qualitatively and quantitatively to interrogate proteins and RNAs carried in intact myeloid-derived suppressor cells (MDSC) and exosomes shed in vitro by MDSC. In aggregate exosomes more than 4000 proteins were identified, including annexins and immunosuppressive mediators. Bioassays showed that exosomes induce MDSC chemotaxis dependent on S100A8 and S100A9 in their cargo. Surface selective chemistry identified glycoproteins on MDSC and exosome surfaces, including CD47 and thrombospondin 1, which both facilitate exosome-catalyzed chemotaxis. Large numbers of mRNAs and microRNAs were identified in aggregate exosomes, whose potential functions in receptor cells include angiogenesis, and proinflammatory and immunosuppressive activities. Inflammation was found to have asymmetric effects on MDSC and exosomal cargos. Collectively, our findings indicate that the exosomes shed by MDSC provide divergent and complementary functions that support the immunosuppression and tumor promotion activities of MDSC.

回顾了合作研究，其中使用基于质谱的蛋白质组学和下一代测序来定性和定量地询问完整骨髓源性抑制细胞 (MDSC) 和 MDSC在体外脱落的外泌体中携带的蛋白质和 RNA。在外泌体中，鉴定出超过 4000 种蛋白质，包括膜联蛋白和免疫抑制介质。生物测定表明，外泌体诱导 MDSC 趋化性依赖于其货物中的 S100A8 和 S100A9。表面选择性化学鉴定了 MDSC 和外泌体表面的糖蛋白，包括 CD47 和血小板反应蛋白 1，它们都促进外泌体催化的趋化性。在聚集的外泌体中鉴定出大量 mRNA 和 microRNA，其在受体细胞中的潜在功能包括血管生成、促炎和免疫抑制活性。研究发现炎症对 MDSC 和外泌体货物具有不对称影响。总的来说，我们的研究结果表明，MDSC 脱落的外泌体提供了不同和互补的功能，支持 MDSC 的免疫抑制和肿瘤促进活性。