TY - JOUR TI - Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes AU - Ku, Amy W AU - Muhitch, Jason B AU - Powers, Colin A AU - Diehl, Michael AU - Kim, Minhyung AU - Fisher, Daniel T AU - Sharda, Anand P AU - Clements, Virginia K AU - O'Loughlin, Kieran AU - Minderman, Hans AU - Messmer, Michelle N AU - Ma, Jing AU - Skitzki, Joseph J AU - Steeber, Douglas A AU - Walcheck, Bruce AU - Ostrand-Rosenberg, Suzanne AU - Abrams, Scott I AU - Evans, Sharon S A2 - Germain, Ronald N VL - 5 PY - 2016 DA - 2016/12/08 SP - e17375 C1 - eLife 2016;5:e17375 DO - 10.7554/eLife.17375 UR - https://doi.org/10.7554/eLife.17375 AB - Myeloid-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. KW - myeloid-derived suppressor cells KW - T cell trafficking KW - lymph node KW - L-selectin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -