In agreement with this, IL-1β-secretion by modified tumor cells leads to the enhanced accumulation of splenic MDSC that potently suppress T-cell proliferation and cytokine secretion 10–12, 16. MDSC enhance tumor growth by several mechanisms including the suppression of the anti-tumor immune response. Mechanisms involving ROS, NO, L-arginine metabolism, nitrotyrosine, secretion of IL-10 and sequestration of cystine/cysteine 14, 16, 17 are involved in mediating

the suppression of T cells, while TGF-β1 is involved in the suppression of NK cells 18. Notably, the expression of ROS by MDSC Ku-0059436 solubility dmso has been correlated with the level of tumor-secreted IL-1β 11. Recent attention focused on the identification of tumor-associated MDSC subpopulations in different tumor models leading to the identification of a granulocytic polymorphonuclear www.selleckchem.com/products/ABT-263.html neutrophil leukocyte (PMN-MDSC) subset as Ly6GhighLy6C+SCChigh and a mononuclear subset characterized as Ly6G−Ly6ChighSCClow (Mon-MDSC 11, 19, 20. Data from Bronte’s group suggest that the immunosuppressive

potential of MDSC cell subsets is sensitive to tumor-derived cytokines such as GM-CSF 21. Together, these studies underscore the heterogeneity within the MDSC-pool with regard to their phenotype and immunosuppressive capacities and that the composition of this pool appears to be dynamically regulated by the tumor microenvironment. NK cells play a major role in tumor immunosurveillance 22, 23. The selleck chemical majority of NK cells are generated in the

bone marrow and after maturation seed peripheral organs. In mice, mature NK cells are defined as CD3−NKp46+ cells expressing CD49b (DX5), CD122 (IL-2 receptor β), NKG2D and Ly49 molecules. CD27, CD11b and KLRG-1 expression divides peripheral NK cells into subsets and available data suggest that cells expressing only CD27+ to be less differentiated than CD27+CD11b+ NK cells, and cells expressing CD11b and KLRG1, but not CD27, may represent the most differentiated NK cells (reviewed in 24, 25). Patients with diverse types of cancer (such as myelogenous leukemia and lung carcinoma) present with NK cell defects, including reduced NK cell numbers, reduced NK cell activity or reduced expression of activating receptors by NK cells 26, 27. Although clinical studies and reports using mouse tumor models have described MDSC suppressing NK cell activities 18, 28, 29, the role of specific MDSC subsets on NK cell suppression remains unclear. In this study, we identify a novel subset of MDSC induced by IL-1β, which lack Ly6C expression and demonstrate enhanced capacity to inhibit NK cell function in vitro and in vivo.