Immunotherapy for human glioma: innovative approaches and recent results

The outcome for malignant glioma patients remains dismal despite treatment with surgical resection, radiation and chemotherapy. The goal of immunotherapy is to eradicate or suppress the residual infiltrative component of these tumors. Although there is clinical evidence for cell-mediated antiglioma activity, there are special considerations that need to be accounted for in the design of immunotherapeutics for CNS tumors, such as possible differences in antigen-presenting cells, trafficking of effector T-cells and immunosuppression. Previously characterized immunosuppression in glioma patients has included low peripheral blood lymphocyte counts, reduced delayed type hypersensitivity reactions to recall antigens, impaired mitogen-induced blastogenic responses by peripheral blood mononuclear cells, increased CD8+ suppressor T-cells, decreased CD4+ T-cell activity in vitro, diminished immunoglobulin synthesis by B-cells and impaired transmembrane signaling through the T-cell receptor/CD3 complex. Recent impairments that are being identified include anergy, failure of costimulation, lack of sufficient numbers of functional effector T-cells and the presence of T-suppressor cells within the tumor microenvironment. It is proposed that these inherent problems will need to be overcome in order for immunotherapies to realize their potential. Paradoxically, the efficacy of recent clinical immunotherapies for glioma patients appears equivalent to that seen in other cancer immunotherapeutic approaches. This review will provide an overview of the juxtaposition of the immune system and CNS, and will discuss the most recent and ongoing immunotherapeutic clinical trials that are demonstrating promising results.