CNSC-101. CHARACTERIZATION OF GBM INDUCED NEURO-IMMUNE AXIS DYSREGULATION

Abstract Glioblastoma (GBM) is the most common and aggressive form of malignant brain tumor in adults. Although GBM is believed to remain localized within the central nervous system (CNS), it exerts systemic effects; most notably, a profound immune suppression. Patients with GBM frequently exhibit lymphopenia, diminished T cell responsiveness, and elevated levels of immunosuppressive myeloid-derived suppressor cells (MDSCs). Through murine studies, our group has previously shown that intracranial gliomas induce changes in the bone marrow, skewing hematopoiesis toward immunosuppressive myeloid lineages at the expense of lymphoid progenitors. This is a striking observation of altered hematopoietic stem cell dynamics, given the anatomical separation between the brain and bone marrow and in lieu of studies of metastatic spread, suggests the presence of a signaling conduit—potentially neural in nature—that enables a novel form of CNS tumor-host communication. Spinal cord and peripheral nerves—particularly the sciatic nerve—represent major neuroimmune interfaces. These regions contain resident immune cells, including microglia and macrophages, that respond dynamically to neuronal activity and injury. These immune cells are capable of producing cytokines, expressing neurotransmitter receptors, and relaying signals that could influence distal organs, including the bone marrow. Considering this, we hypothesize that GBM induces disruption of neuroimmune signaling pathways that alters the phenotype and function of peripheral immune cells and hematopoietic progenitors. To investigate this, we have identified and characterized genotypic and phenotypic GBM-associated changes in spinal and peripheral nerve tissues. We have also probed the spinal and peripheral nerve tissues to assess variances in population, spatial distribution and expression of key neurotransmitter receptors of the immune cells within them.