Adv Exp Med Biol
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Glioblasotmas are the most common primary central nervous system tumor and typically have a dismal prognosis. Immunotherapy has been a promising experimental treatment. Understanding brain tumor immunobiology is critical to designing glioblasotma immunotherapies. ⋯ The antigenic underpinnings of brain tumor immunotherapy including glioma-associated and glioma-specific antigens are discussed. Finally, the molecular and cellular facets of glioma-mediated immunosuppression are outlined. The role of multiple cell types (glioma cells, glioma-infiltrating monocytes, regulatory T cells and myeloid derived suppressor cells) in mediating local and systemic immunosuppression in glioma patients is evaluated.
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Immunological effector cells and molecules have been shown to access intracranial tumor sites despite the existence of blood brain barrier (BBB) or immunosuppressive mechanisms associated with brain tumors. Recent progress in T-cell biology and tumor immunology made possible to develop strategies of tumor-associated antigen-specific immunotherapeutic approaches such as vaccination with defined antigens and adoptive T-cell therapy with antigen-specific T cells including gene-modified T cells for the treatment of patients with brain tumors. ⋯ Nevertheless, treatment with lymphocytes that are engineered to express tumor-specific receptor genes is a promising immunotherapy against glioma, based on the significant efficacy reported in the trials for patients with other types of malignancy. Overcoming the relative difficulty to apply immunotherapeutic approach to intracranial region, current advances in the understanding of human tumor immunology and the gene-therapy methodology will address the development of effective immunotherapy of brain tumors.