My research program relates to brain cancer biology, development of immune-therapeutics for primary and metastatic brain cancer; manipulating the brain tumor microenvironment; in vivo migration of immune cells into the brain and the tumor mass; the role of pattern recognition receptors’ signaling in cancer immune suppression and brain inflammation. Mechanisms mediated by myeloid derived suppressor cells (MDSCs) in brain cancer biology and response to therapeutics. We are investigating the molecular and cellular mechanisms underlying tumor regression and immunological memory in pre-clinical models of glioblastoma (GBM) and metastatic brain cancer. We uncovered the role of plasmacytoid dendritic cells as antigen presenting cells (APCs) within the brain; uptake of tumor antigens in the tumor microenvironment, migration to the draining lymph node and triggering an effective adaptive anti-tumor immune response, resulting tumor regression and anti-tumor immunological memory. Using knockout mice models and bone marrow adoptive transfer technologies, we uncovered that the immune cells within the tumor microenvironment which are responsible for tumor immunity are bone marrow (BM) derived. We elucidated the role played by Toll-like receptor 2 (TLR2) signaling on BM derived, tumor infiltrating dendritic cells (DCs) in mediating tumor regression and anti-tumor immunological memory in response to combined conditional cytotoxic/immune-stimulatory gene therapy. TLR2 activation was elicited by an endogenous, tumor-derived TLR ligand, i.e., HMGB1 (a transcription factor that binds to DNA in live cells) released from dying cancer cells. Circulating HMGB1 could be used as a biomarker for therapeutic efficacy. We are investigating the mechanisms by which circulating HMGB1 mediates immune cells’ trafficking into the tumor microenvironment and anti-tumor immunity. Mechanisms of trafficking and homing of immune cells in preclinical cancer models will uncover novel therapeutic strategies.