Differential Content of Proteins, mRNAs, and miRNAs Suggests that MDSC and Their Exosomes May Mediate Distinct Immune Suppressive Functions

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dc.contributor.authorGeis-Asteggiante, Lucía
dc.contributor.authorT. Belew, Ashton
dc.contributor.authorClements, Virginia K.
dc.contributor.authorEdwards, Nathan J.
dc.contributor.authorOstrand-Rosenberg, Suzanne
dc.contributor.authorEl-Sayed, Najib M.
dc.contributor.authorFenselau, Catherine
dc.date.accessioned2019-03-04T16:32:40Z
dc.date.available2019-03-04T16:32:40Z
dc.date.issued2018-10-24
dc.description.abstractMyeloid-derived suppressor cells (MDSC) are immature myeloid cells that accumulate in the circulation and the tumor microenvironment of most cancer patients. There, MDSC suppress both adaptive and innate immunity, hindering immunotherapies. The inflammatory milieu often present in cancers facilitates MDSC suppressive activity, causing aggressive tumor progression and metastasis. MDSC from tumor-bearing mice release exosomes, which carry biologically active proteins and mediate some of the immunosuppressive functions characteristic of MDSC. Studies on other cell types have shown that exosomes may also carry RNAs which can be transferred to local and distant cells, yet the mRNA and microRNA cargo of MDSC-derived exosomes has not been studied to date. Here, the cargo of MDSC and their exosomes was interrogated with the goal of identifying and characterizing molecules that may facilitate MDSC suppressive potency. Because inflammation is an established driving force for MDSC suppressive activity, we used the well-established 4T1 mouse mammary carcinoma system, which includes “conventional” as well as “inflammatory” MDSC. We provide evidence that MDSC-derived exosomes carry proteins, mRNAs, and microRNAs with different quantitative profiles than those of their parental cells. Several of these molecules have known or predicted functions consistent with MDSC suppressive activity, suggesting a potential mechanistic redundancy.en_US
dc.description.sponsorshipL.G.-A., V.K.C, N.J.E., S.O.-R., and C.F. are supported by the National Institutes of Health Grants GM021248 and OD019938. L.G.-A. is additionally supported by the University of Maryland Ann G. Wylie Dissertation Fellowship. A.T.B. and N.M.E. are funded, in part, by NIH Grant AI094773. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.en_US
dc.description.urihttps://pubs.acs.org/doi/10.1021/acs.jproteome.7b00646en_US
dc.format.extent13 pagesen_US
dc.genrejournal articles postprintsen_US
dc.identifierdoi:10.13016/m2k5h8-skhf
dc.identifier.citationLucía Geis-Asteggiante, Ashton T. Belew, Virginia K. Clements, Nathan J. Edwards, Suzanne Ostrand-Rosenberg, Najib M. El-Sayed, and Catherine Fenselau,Differential Content of Proteins, mRNAs, and miRNAs Suggests that MDSC and Their Exosomes May Mediate Distinct Immune Suppressive Functions, Journal of Proteome Research 2018 17 (1), 486-498 DOI: 10.1021/acs.jproteome.7b00646en_US
dc.identifier.urihttps://dx.doi.org/10.1021%2Facs.jproteome.7b00646
dc.identifier.urihttp://hdl.handle.net/11603/12909
dc.language.isoen_USen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Biological Sciences Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.jproteome.7b00646
dc.subjectdifferential expressionen_US
dc.subjectexosomesen_US
dc.subjectmiRNAen_US
dc.subjectmRNAen_US
dc.subjectmyeloid-derived suppressor cellsen_US
dc.subjectnext generation sequencingen_US
dc.subjectshotgun proteomicsen_US
dc.titleDifferential Content of Proteins, mRNAs, and miRNAs Suggests that MDSC and Their Exosomes May Mediate Distinct Immune Suppressive Functionsen_US
dc.typeTexten_US

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