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.
Keywords: Exosomes; Immune suppression; Inflammation; Myeloid-derived suppressor cells; Proteoforms; Proteomics; RNAs; Small extracellular vesicles; Surface glycoproteins; Ubiquitination.
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