Frontiers in the Immunology of Brain Tumors

Dear Colleagues,

Antigenic differences between the normal and malignant cells of cancer patients form the rationale for clinical immunotherapeutic strategies. While the central nervous system has traditionally been thought of as an immune-privileged site, a number of studies have been conducted that demonstrate the potential efficacy of immunotherapy in management of primary and secondary brain tumors. A variety of strategies have been used to increase the immunogenetic properties of vaccine therapies for brain tumors. One emerging strategy in the treatment of tumors involves the stimulation of an immunologic response against neoplastic cells. Tumor cells may evade immune responses by disrupting the expression of antigens or major histocompatibility complex (MHC) molecules. The immune response can be augmented by genetic modification of tumor cells to secrete cytokines, including IL-2, GM-CSF, and interferon-γ. Alternatively, one can genetically modify the tumor cells to express co-stimulatory molecules such as B7. The modification of neoplastic cells taken directly from tumor-bearing patients may be difficult. An alternative cell type that can be used for therapeutic immunizations is the dendritic cell (DC), which is a specialized antigen-presenting cell. Preclinical studies have indicated that immunization with DC pulsed with tumor cell antigens can stimulate a cytotoxic T cell response that is tumor-specific and engenders protective immunity against CNS tumors. Another strategy is to transfect genomic DNA from the malignant cells into a fibroblast cell line, which results in stable integration and expression of the transferred DNA. Immunization of tumor-bearing mice with the DNA-based vaccine results in the induction of cell-mediated immunity directed toward the type of tumor from which the DNA was obtained along with prolongation of survival. Finally, regulation of immune checkpoint inhibitors, which are capable of blocking molecules involved in inhibiting immune cells, can result in a stimulation of the T-cell response against various tumors, including brain tumors.

The ultimate goal of cancer therapy is the elimination of every remaining tumor cell from the patient. It is unlikely that a single form of therapy is capable of achieving this goal. However, immunotherapy in combination with surgery, radiation therapy, and chemotherapy will likely find a place as a new and important means of treatment for patients with brain tumors. Although the utilization of immunotherapeutic strategies has proven efficacious against a variety of tumors, immunotherapy for the treatment of brain tumors has resulted in mixed success, with conflicting research findings. Certainly, more work in this field is critically needed. For this Special Issue, papers are being solicited that explore the potential of different immunotherapeutic strategies for the treatment of brain tumors along with related aspects of tumor immunotherapy.

Dr. Terry Lichtor
Guest Editor

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• brain tumors
• gliomas
• immunotherapy
• gene therapy