as we show here, or proinflammatory Th17 cells, given that Treg differentiation can be diverted to Th17 differentiation in the presence of IL-6. It will be important for future studies to elucidate the celltype specific contributions of Adora2b in controlling both acute and chronic inflammatory responses. The central role of Adora2b in determining the outcome of both acute and chronic pathologies SCH772984 Abmole Analgesic effect and possible mechanism of SCH772984 intrathecal injection on rats with bone cancer pain identifies this molecule as a promising point of intervention. Since Adora2b serves as a receptor both for extracellular adenosine as well as for alternative ligands, this receptor may function to integrate multiple extrinsic cues to promote Tregs to restrict the duration and magnitude of inflammation. Pharmacologic targeting of adenosine pathways such as Adora2b may also synergize with modalities that activate the hypoxic response and have been shown to be tissue-protective in models of colitis. Conversely, since both Adora2a and Adora2b signaling promote Tregs, transient depletion of extracellular adenosine through the administration of pegylated-ADA may be a potent method to transiently limit the generation or activity of Tregs. Based on the potential of Adora2b-targeted treatments to modulate regulatory T cells, future studies will interrogate the consequences and therapeutic benefits of manipulating the Adora2b-Treg axis in both acute and chronic states of inflammation. Malignant brain tumors are a devastating disease with a high mortality rate. These tumors do not have defined boundaries and complete surgical removal is virtually impossible. In addition, the intrinsic heterogeneity and genetic instability in these tumors results in cells resistant to therapy. Thus, even after INC280 Abmole Heterogeneous Stromal Signaling within the Tumor Microenvironment Controls the Metastasis of Pancreatic Cancer surgery, radiation and chemotherapy these tumors typically recur, leading to patient mortality and an average survival of approximately 1.5 years. Increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available therapies and/or limit tumor growth. Advances in our understanding of the biology of these tumors has led to an increase in the number of targeted therapies in preclinical and clinical. While these therapies may prove somewhat effective, the heterogeneity of this tumor often precludes the targeted molecules from being found on all cells in the tumor thus reducing the efficacy of these treatments. In contrast, one trait shared by virtually all tumor cells is altered metabolism. Metabolic dysregulation of cancer cells was first described in the 1950s by Otto Warburg, who identified differences in glucose uptake and production of lactate between non-neoplastic and neoplastic cells.