Immunotherapy in Glioblastoma: Current Shortcomings and Future Perspectives

• Published in: Cancers Vol. 12; no. 3; p. 751
• Main Authors: Weenink, Bas, French, Pim J, Sillevis Smitt, Peter A E, Debets, Reno, Geurts, Marjolein
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-03-2020; MDPI
• Subjects: Antigens; Brain cancer; Brain tumors; Cancer therapies; CD8 antigen; Cell activation; Central nervous system; Chemotherapy; Dendritic cells; Genes; Glioblastoma; Immune checkpoint inhibitors; Immune privilege; Immunogenicity; Immunotherapy; Lung cancer; Lymphocytes; Lymphocytes T; Lymphoma; Medical prognosis; Melanoma; Mutation; Patients; Peptides; Proteins; Radiation therapy; T cell receptors; Temozolomide; Tumors; Vaccines; Vascular endothelial growth factor; adoptive T cell therapy; glioblastoma; vaccines; clinical studies; tumor micro-environment; antigens; immune privilege; checkpoint inhibitors
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12030751

Glioblastomas are aggressive, fast-growing primary brain tumors. After standard-of-care treatment with radiation in combination with temozolomide, the overall prognosis of newly diagnosed patients remains poor, with a 2-year survival rate of less than 20%. The remarkable survival benefit gained with immunotherapy in several extracranial tumor types spurred a variety of experimental intervention studies in glioblastoma patients. These ranged from immune checkpoint inhibition to vaccinations and adoptive T cell therapies. Unfortunately, almost all clinical outcomes were universally disappointing. In this perspective, we provide an overview of immune interventions performed to date in glioblastoma patients and re-evaluate their performance. We argue that shortcomings of current immune therapies in glioblastoma are related to three major determinants of resistance, namely: low immunogenicity; immune privilege of the central nervous system; and immunosuppressive micro-environment. In this perspective, we propose strategies that are guided by exact shortcomings to sensitize glioblastoma prior to treatment with therapies that enhance numbers and/or activation state of CD8 T cells.