Immunotherapy for Glioma: From Illusion to Realistic Prospects?

Abstract

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.KEY POINTSMultipeptide vaccines and cell therapy with engineered T lymphocytes are promising strategies for patients with glioma.The selection of antigens targeted by immune effectors must be extremely rigorous to avoid unacceptable damage in the context of the brain.Reshaping the brain tumor microenvironment is required to ensure optimal efficacy of immune effector cells.Emerging data indicate that synergies with immune checkpoint inhibitors and chemotherapy must be exploited.Multiples challenges remain, but using the immune system to fight glioma is now a realistic prospect.