Mechanisms of local immunoresistance in glioma

Even though the central nervous system (CNS) was conventionally defined as "immunologically privileged", new discoveries have demonstrated the role of the immune system in neurologic disease and illness, including gliomas. Brain tumor immunotherapy is an exciting and revived area of research, in which neurosurgeons have taken a major position. Despite the ability to induce a tumor-specific systemic immune response, the challenge to effectively eradicate intracranial gliomas remains mainly because of tumor-induced immunoresistance. This article gives an overview of the immunologic responses that occur in the CNS and their potential role in brain tumors. The main cellular and molecular mechanisms that mediate tumor escape from natural immune surveillance are also covered in this article. Glioma cells have been shown to diminish the expression of danger signals necessary for immune activation and to increase the concentration of immunosuppressive factors in the tumor microenvironment, which results in T-cell anergy or apoptosis. Finally, the authors discuss most of the over-expressed oncogenic signaling pathways that cause tumor tolerance.