Immunotherapy in glioblastoma treatment: Current state and future prospects

Abstract

Glioblastoma remains as the most common and aggressive malignant brain tumor, standing with a poor prognosis and treatment prospective. Despite the aggressive standard care, such as surgical resection and chemoradiation, median survival rates are low. In this regard, immunotherapeutic strategies aim to become more attractive for glioblastoma, considering its recent advances and approaches. In this review, we provide an overview of the current status and progress in immunotherapy for glioblastoma, going through the fundamental knowledge on immune targeting to promising strategies, such as Chimeric antigen receptor T-Cell therapy, immune checkpoint inhibitors, cytokine-based treatment, oncolytic virus and vaccine-based techniques. At last, it is discussed innovative methods to overcome diverse challenges, and future perspectives in this area.

Keywords: Brain cancer; Chimeric antigen receptor T cell; Glioblastoma; Immune-checkpoint inhibitors; Immunotherapy; Oncolytic viruses; Tumor microenvironment.

Figure 1

Scheme about current glioblastomas treatment strategies and its advantages and limitations. GBM: Glioblastomas; OS: Overall survival; PFS: Progression-free survival; TMZ: Temozolomide; VEGF: Vascular endothelial growth factor;

Figure 2

Simplified scheme of glioblastomas-induced immunosuppressive microenvironment. MDSCs: myeloid-derived suppressor cells; NK: Natural killer. The Figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license.

Figure 3

Immune checkpoint inhibition targets: T cell immunoglobulin and mucin domain 3/ Galactin 9, programmed cell death-1/programmed death-ligand 1, and cytotoxic T-lymphocyte-associated protein 4 /CD80 or CD86. A: T cell immunoglobulin and mucin domain 3/ Galactin 9; B: programmed cell death-1/programmed death-ligand 1; C: cytotoxic T-lymphocyte-associated protein 4/CD80 or CD86. TIM-3: T cell immunoglobulin and mucin domain 3; GAL-9: Galactin 9; PD-1: Programmed cell death-1; PDL-1: Programmed death-ligand 1; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4. The Figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license.

Figure 4

Simplified scheme of oncolytic virotherapy for glioblastomas. GBM: Glioblastoma; OV: Oncolytic virus; PAMPs: Pathogen-associated molecular patterns; DAMPs: Damage-associated molecular patterns. The Figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license.