Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes

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dc.contributor.authorKu, Amy W.
dc.contributor.authorMuhitch, Jason B.
dc.contributor.authorPowers, Colin A.
dc.contributor.authorDiehl, Michael
dc.contributor.authorKim, Minhyung
dc.contributor.authorFisher, Daniel T.
dc.contributor.authorSharda, Anand P.
dc.contributor.authorClements, Virginia K.
dc.contributor.authorO'Loughlin, Kieran
dc.contributor.authorMinderman, Hans
dc.contributor.authorMessmer, Michelle N.
dc.contributor.authorMa, Jing
dc.contributor.authorSkitzki, Joseph J.
dc.contributor.authorSteeber, Douglas A.
dc.contributor.authorWalcheck, Bruce
dc.contributor.authorOstrand-Rosenberg, Suzanne
dc.contributor.authorAbrams, Scott I.
dc.contributor.authorEvans, Sharon S.
dc.date.accessioned2019-03-04T15:09:56Z
dc.date.available2019-03-04T15:09:56Z
dc.date.issued2016-12-08
dc.description.abstractMyeloid-derived suppressor cells (MDSC) contribute to an immunosuppressive network that drives cancer escape by disabling T cell adaptive immunity. The prevailing view is that MDSC-mediated immunosuppression is restricted to tissues where MDSC co-mingle with T cells. Here we show that splenic or, unexpectedly, blood-borne MDSC execute far-reaching immune suppression by reducing expression of the L-selectin lymph node (LN) homing receptor on naïve T and B cells. MDSC-induced L-selectin loss occurs through a contact-dependent, post-transcriptional mechanism that is independent of the major L-selectin sheddase, ADAM17, but results in significant elevation of circulating L-selectin in tumor-bearing mice. Even moderate deficits in L-selectin expression disrupt T cell trafficking to distant LN. Furthermore, T cells preconditioned by MDSC have diminished responses to subsequent antigen exposure, which in conjunction with reduced trafficking, severely restricts antigen-driven expansion in widely-dispersed LN. These results establish novel mechanisms for MDSC-mediated immunosuppression that have unanticipated implications for systemic cancer immunity.en_US
dc.description.sponsorshipWe thank C Netherby for technical assistance on the mammary fat pad model and M Appenheimer for critical reading of the manuscript. This work was supported by the NIH (CA79765 and AI082039 to SS Evans; T32 CA085183 to AW Ku; 5 T32 CA108456 to CA Powers; CA203348 to B Walcheck; GM021248 and CA115880 to S Ostrand-Rosenberg; CA140622 and CA172105 to SI Abrams; 1R50CA211108 to H Minderman); the University at Buffalo Mark Diamond Research Fund (to AW Ku); the Jennifer Linscott Tietgen Family Foundation (to SS Evans and JJ Skitzki); and the Breast Cancer Coalition of Rochester (to SS Evans and SI Abrams). Cytometry services were provided by the Flow and Image Cytometry Shared Resource facility at the Roswell Park Cancer Institute which is supported, in part, by the NCI Cancer Center Support Grant 5P30 CA016056.en_US
dc.description.urihttps://elifesciences.org/articles/17375en_US
dc.format.extent29 pagesen_US
dc.genrejournal articlesen_US
dc.identifierdoi:10.13016/m220wq-dp1k
dc.identifier.citationAmy W Ku, Jason B Muhitch, Colin A Powers, Michael Diehl, Minhyung Kim, et.al, Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes, eLife 2016; 5:e17375, DOI: 10.7554/eLife.17375en_US
dc.identifier.urihttps://doi.org/10.7554/eLife.17375
dc.identifier.urihttp://hdl.handle.net/11603/12904
dc.language.isoen_USen_US
dc.publishereLife Sciences Publications Ltden_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.rightsAttribution 4.0 International (CC BY 4.0)*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectMyeloid-derived suppressor cells (MDSC)en_US
dc.subjectT cellen_US
dc.subjectL-selectin lymph node (LN)en_US
dc.subjectADAM17en_US
dc.titleTumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodesen_US
dc.typeTexten_US

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