Immunotherapy: Present and future directions

The role of immunotherapy in oncology has rapidly expanded over the past century. The old paradigm posited the brain to be an "immune-privileged" location, as the tumor microenvironment has been shown to be highly immunosuppressive in nature. However, more recent observations have paved the way for the use of immunotherapy in neurooncology. Immuno-modulation represents a promising treatment paradigm in conjunction with standard of care therapy that has the potential to greatly improve morbidity and mortality in patients with high-grade gliomas. Various targeted treatment modalities have arisen and include surface-directed immunotherapies, adoptive lymphocyte transfer, vaccines, and immune checkpoint blockade. Each treatment modality seeks to take advantage of tumor biology. Surfacedirected immunotherapies exploit over-expressed cell surface receptors on tumor cells. Adoptive lymphocyte transfer employs cytotoxic antigen-specific T-cells against tumors. Vaccines enhance the host antigen-specific anti-tumor immune response with minimal side effects. Finally, immune checkpoint blockade seeks to reverse tumor-mediated T-cell exhaustion and restore the host anti-tumor immune response. Each of these therapies has demonstrated successful anti-tumor immune-mediated responses in pre-clinical and clinical models, alike. Despite such success, multiple challenges to implementation and optimization of immunotherapy remain. For instance, small cohorts and molecularly unique tumors preclude broader generalizations. Additionally, dynamic tumor biology once susceptible to one immunotherapy modality may become resistant to the same treatment approach over time. However, immunotherapy has demonstrated a proven role established by myriad pre-clinical and clinical studies. Future work will investigate the promising role of combining immunotherapy with the current standard of care in the hopes of improving morbidity and mortality.