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.

Additional Metadata
Keywords adoptive T cell therapy, antigens, checkpoint inhibitors, clinical studies, glioblastoma, immune privilege, tumor micro-environment, vaccines
Persistent URL dx.doi.org/10.3390/cancers12030751, hdl.handle.net/1765/128724
Journal Cancers
Citation
Weenink, B., French, P.J, Smitt, P., Debets, J.E.M.A, & Geurts, M. (2020). Immunotherapy in Glioblastoma: Current Shortcomings and Future Perspectives. Cancers, 12(3). doi:10.3390/cancers12030751