Characterization of microglia phenotype and function within malignant human gliomas: A potential mechanism for immune anergy

5311 Microglia play a critical role in mediating potent immune responses to traumatic, infectious or degenerative challenges in the human brain. However, during the growth of malignant gliomas, microglia infiltrate the tumor in increased numbers yet fail to inhibit tumor growth. Little is known about the performance and interactions of these cells in a tumor microenvironment, including any possible impairment of their functions. Here we provide a novel characterization of the immune phenotype and function of human glioma-infiltrating microglia (GIM) immediately isolated from tumors post-surgical resection. GIM were isolated from tumor homogenate by sequential percoll gradient purification and identified based on established parameters (CD45 low CD11b/c + ). They expressed significant levels of MHC class II on their surface but minimal levels of the co-stimulatory molecules CD80, CD83, CD86 and CD40 suggesting that GIM may induce immunological anergy in effector T cells. The expression of FasL was low to absent, indicating that apoptosis of the incoming lymphocyte population may not be a predominant mode of immunosupression. The GIM expressed FcR II and FcR III, necessary for mediating antibody dependent cellular cytotoxicity (ADCC). Intracellular cytokine staining demonstrated production of IL-6 and IL-12. In addition, GIM were capable of phagocytosis and tumor cytotoxicity in the absence of any in vitro stimulation. Characterization of GIM provides novel insight into their innate as well as adaptive immune function, thereby contributing to the design and optimization of immunotherapeutic strategies against malignant brain tumors.