Innate immune functions of microglia isolated from human glioma patients

Abstract

Background: Innate immunity is considered the first line of host defense and microglia presumably play a critical role in mediating potent innate immune responses to traumatic and infectious challenges in the human brain. Fundamental impairments of the adaptive immune system in glioma patients have been investigated; however, it is unknown whether microglia are capable of innate immunity and subsequent adaptive anti-tumor immune responses within the immunosuppressive tumor micro-environment of human glioma patients. We therefore undertook a novel characterization of the innate immune phenotype and function of freshly isolated human gliomainfiltrating microglia (GIM).

The treatment of glioblastoma multiforme through activation of microglia and TRAIL induced by rAAV2-mediated IL-12 in a syngeneic rat model

“…Actively growing tumors can prevent activated microglia from secretion of cytotoxic and apoptosis-associated cytokines [15,26]. However, our use of rAAV2/IL12 that increased the intracerebral concentrations of IL-12 and IFN-γ (Figures 1 and 2) and microglial infiltration (Figures 3, 4, 5 and 6) modulated the tumor environment, and restored the defensive function of the microglia.…”

Immune therapeutic targeting of glioma cancer stem cells

“…Although activated microglia are effective mediators of innate immunity, capable of phagocytosis, cytotoxicity, antigen presentation, and promotion of inflammation [60, 61], this function is impaired within the context of malignant gliomas. For example, glioma-infiltrating microglia do not express the costimulatory molecules necessary for effective antigen presentation [58] and are unable to secrete proinflammatory cytokines [62]. Instead, they can actually support GBMs by mediating angiogenesis, proliferation, and tissue invasion [63] and become similar to other tumor-associated macrophages found in many other malignancies [64].…”

Immune Connection in Glioma: Fiction, Fact and Option

“…Activation of microglia via Toll-like receptors (TLRs) were also insignificant to augment tumoricidal activity (Hussain et al, 2006a). Particularly, proinflammatory cytokines including IL-1 , IL-6, TNF could not be sufficiently released to launch substantial innate immune function against glioma, however their phagocytic function was not impaired and also exhibited low level of non-specific cytotoxicity (Hussain et al, 2006b). In rodent glioma model lack of proinflammatory cytokines IFN , IL-12 and IL-6, and conversely cumulative dominance of IL-4 and IL-10 favoring the suppression of immune response was recently observed (Ghosh et al, 2010).…”