Stat3 interactions in glioma biology. There is evidence for a role for Stat3 in tumor cells, immune cells and endothelial cells within gliomas. Stat3 mediated proliferative/survival signals downstream of LIF or IL-6. It also possibly mediates differentiation downstream of BMP/mTOR activation. Several genetic and epigenetic mutations/interactions which impact the Stat3 pathway have been documented, including mutations in the EGFR, hypermethylation of SOCS and BMPR promoters and misregulation of several miRNAs including miR326 which affects notch signals. Stat3 also appears to be an important regulator of mesenchymal transformation events. These interactions are impacted by levels of ERK and notch signals present within the cells. Inflammation results in the activation of several pathways which impinge directly on levels of activated Stat3. These include upregulation of notch signaling and recruitment of OSM and IFNγ mediated signals. Stat3 plays an important role in the immunotolerance of the tumor by the host. It also is involved in the production of angiogenic factors in the tumor microenvironment, and in the mediation of VEGF signaling in endothelial cells within the tumor.