Microglia are brain tissue resident monocytes that are responsible for innate immunity in the brain. In the aging and degenerative brain, especially late onset Alzheimer disease (LOAD), resting microglia are activated by amyloid beta (Aß) accumulation and amyloid plaques. Local chronic inflammatory environment in LOAD contain proinflammatory and anti-inflammatory cytokines such as stromal cell derived factor-1 (SDF-1), transforming growth factor ß1 (TGF-ß1), and interferon-γ, all regulate the activity of microglia by increasing neuroprotection or impairing phagocytosis of Aß via interacting with receptors on the microglia.
In gliomas, microglia constitute large proportion of tumor mass and support the expansion and invasion of glioma cells, especially in glioblastomas (GBM). GBM is morphologically characterized by necrosis, and chronic inflammation surrounding the necrotic areas and in tumor cells. Glioma cells attract and reprogram microglia through common microglia receptors seen in LOAD such as CXCR4 and TGF-ß1. Glioma associated microglia exhibit M2 phenotype. Given the fact that most primary GBM arise in old age patients whose brain exhibit a trait of degenerative morphology and revealing pathology of localized chronic neuroinflammation. It is worth investigating the role of microglia on how it inhibits or enhances glioma progression in the aged or degenerative brain microenvironment.
This talk will encompass recent progress of neuroimmunology and immunotherapy in CNS diseases, with emphasis on utilizing microglia as an effector cell and immune signaling targets on microglias in treating Alzheimer’s disease and GBM. We will also introduce possible unprecedented combinatorial immunotherapeutic strategies against GBM and in preventing LOAD progression. |
