Immunotherapy for glioma: from illusion to realistic prospects?

There is now evidence that the rules established for tumor immunology and immunotherapy in general are relevant for brain tumors. Treatment strategies explored have mainly involved vaccines using either tumor cells or components, and vaccines with defined synthetic peptides. This latter approach offers the advantage to select well-characterized antigens with selective or preferential expression on glioma. This is a prerequisite because collateral damage to the brain is not allowed. A second strategy which is reaching clinical trials is T cell therapy using the patients' own lymphocytes engineered to become tumor reactive. Tumor specificity can be conferred by forced expression of either a high-avidity T cell receptor or an antitumor antibody (the latter cells are called chimeric antigen receptors). An advantage of T cell engineering is the possibility to modify the cells to augment cellular activation, in vivo persistence and resistance to the tumor immunosuppressive milieu. A direct targeting of the hostile glioma microenvironment will additionally be required for achieving potent immunotherapy and various trials are assessing this issue. Finally, combining immunotherapy with immune checkpoint inhibitors and chemotherapy must be explored within rigorous clinical trials that favor constant interactions between the bench and bedside. Regarding immunotherapy for glioma patients, what was an unrealistic dream a decade ago is today a credible prospect.