Bottlenecks and opportunities in immunotherapy for glioma:a narrative review

Glioma is the most aggressive brain tumor having invasive ability and a highly heterogeneous phenotype.Many patients with glioma respond poorly to traditional surgery or temozolomide-based chemotherapy.Over the past few decades,developments in immunotherapeutic strategies have provided newer insights into the treatment of gliomas.Immunotherapy is based on the principle of normalization or recovery of T cell-mediated anti-tumor immunoreaction.Different innovative strategies have been used;these include enhancement of immunogenicity by administration of tumor antigens or dendritic cell vaccines,replenishment of cytotoxic T cells by adoptive T cell transfer,repair of exhausted T cells by immune checkpoint inhibitors,and the use of other immune activators such as oncolytic viruses.However,many immunotherapy-based clinical trials did not meet the expected therapeutic endpoints in patients with glioma.Gliomas use unique strategies to generate an immune-suppressive microenvironment;these include limiting immunogenicity and repressing T cell infiltration or activation.This may be addressed by the incorporation of immunotherapy with standard therapy or by use of certain innovative approaches such as tumor-treating fields.In this review,we summarize the updated immunotherapies in glioma and discuss current limitations and future prospects.