Ku, Amy W.Muhitch, Jason B.Powers, Colin A.Diehl, MichaelKim, MinhyungFisher, Daniel T.Sharda, Anand P.Clements, Virginia K.O'Loughlin, KieranMinderman, HansMessmer, Michelle N.Ma, JingSkitzki, Joseph J.Steeber, Douglas A.Walcheck, BruceOstrand-Rosenberg, SuzanneAbrams, Scott I.Evans, Sharon S.2019-03-042019-03-042016-12-08Amy 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.17375https://doi.org/10.7554/eLife.17375http://hdl.handle.net/11603/12904Myeloid-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.29 pagesen-USThis 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.Attribution 4.0 International (CC BY 4.0)https://creativecommons.org/licenses/by/4.0/Myeloid-derived suppressor cells (MDSC)T cellL-selectin lymph node (LN)ADAM17Text