Immune response: Glioma-associated immunosuppression

Gliomas such as glioblastoma have a complex relationship with the immune system. Glioblastomas have a harshly immunosuppressive microenvironment due in large part to the expression of multiple factors by tumor cells that inhibit T-cell responses. In addition, glioblastomas are heavily infiltrated with monocytic cells. These cells appear to have become immunosuppressive under the influence of the tumor and share characteristics with myeloid-derived suppressor cells. To a lesser degree, gliomas have T-cell infiltrates. Similarly, these largely appear to have adopted the immunosuppressive phenotype of regulatory T cells. Glioblastoma patients also have marked systemic immunosuppression characterized by globally reduced T-cell counts and impaired T-cell function coupled with increased circulating immunosuppressive regulatory T cells and myeloid-derived suppressor cells. The relationships between these various immunosuppressive cell populations, their impact on T cells, and their implications for immunotherapies are reviewed in this chapter.