Browsing by Subject "Myeloid-derived suppressor cells (MDSC)"
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Item Myeloid Derived-Suppressor Cells: Their role in cancer and obesity(Elsevier, 2018-04) Ostrand-Rosenberg, SuzanneMyeloid-derived suppressor cells (MDSC) are present in most individuals with cancer where they inhibit adaptive and innate antitumor immunity and are an obstacle to cancer immunotherapies. Chronic inflammation is characteristic of adipose tissue and is a risk factor for the onset and progression of cancer in obese individuals. Because MDSC accumulate in response to inflammation, it has been hypothesized that one of the mechanisms by which obesity promotes malignancy is through the induction of MDSC. This article reviews the data supporting this hypothesis, the role of leptin and fatty acid metabolism in the induction of MDSC, and the surprising finding that although MDSC promote tumor progression, they are protective against some of the metabolic dysfunction associated with obesity.Item Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes(eLife Sciences Publications Ltd, 2016-12-08) Ku, Amy W.; Muhitch, Jason B.; Powers, Colin A.; Diehl, Michael; Kim, Minhyung; Fisher, Daniel T.; Sharda, Anand P.; Clements, Virginia K.; O'Loughlin, Kieran; Minderman, Hans; Messmer, Michelle N.; Ma, Jing; Skitzki, Joseph J.; Steeber, Douglas A.; Walcheck, Bruce; Ostrand-Rosenberg, Suzanne; Abrams, Scott I.; Evans, Sharon S.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.