Glioblastomas are malignant tumors that affect the brain or spinal cord. These tumors arise from astrocytes, but after forming are usually composed of many different cell types. This mixed-cell feature of glioblastomas contributes to the difficulty in developing newer successful treatments. Radiation and chemotherapy remain as first-line treatments for glioblastomas. Targeted therapies (drugs designed to block molecules that promote tumor growth and progression) that have been developed thus far have not yet yielded very promising outcomes for patients with glioblastomas and are associated with a number of troublesome side effects.
Advances in the understanding of the immune system have uncovered information that can improve the utility of immunotherapy for glioblastomas. Immunotherapeutic approaches are promising because they are based on using the body's own immune cells and factors to combat cancer. This approach has shown positive outcomes in patients with melanoma, lung, and bladder cancer. The case for glioblastoma has been challenging due to the mixed-cell makeup and the differences in how these tumors develop.
Reports of the role of cytotoxic T cells in glioblastoma are promising. There have been a few cases in which a therapy using CAR-T cells targeting interleukin (IL)-13R2a provided strong and lasting therapeutic responses when injected directly into patients' glioblastoma tumors. Research also revealed that an imbalance in the regulatory T cell−cytotoxic T cell ratio leads to an inhibition of anti-tumor immune responses in patients with glioblastoma. Approaches to block a T-cell surface protein, PD-1 (a checkpoint protein), that suppresses T-cell inflammatory activity have been studied for their effects on glioblastomas. However, combining this approach with the use of cancer vaccines may be more advantageous because glioblastomas only weakly induce the cytotoxic T cell response.
Combining cytotoxic immunotherapies that use viral vectors with immune checkpoint inhibition may better activate T cells against glioblastoma tumors. Research that explores the nature of glioblastoma immunology can help provide the key information needed to design multi-agent therapies that can be effective against these aggressive and hard-to-treat tumors. The ongoing and worldwide study of immunotherapy for cancers continues to be promising and can lead to viable treatments with significantly reduced adverse side effects.
Reardon DA, e. (2018). Immunotherapy for glioblastoma: on the sidelines or in the game? - PubMed - NCBI. Ncbi.nlm.nih.gov. Retrieved 10 January 2018, from https://www.ncbi.nlm.nih.gov/pubmed/29278673