Immunomodulation: checkpoint blockade etc.: Fig. 1.

Abstract

The immune microenvironment is considered a major obstacle to generating an effective antitumor immune response. Checkpoint inhibitors manipulate the co-stimulatory response between antigen-presenting cells and immune cells-or between the tumor and immune cells-to elicit an antitumor immune response that would have otherwise been suppressed. Checkpoint inhibitors have shown great promise in the clinics, and some inhibitors such as anti-CTLA-4 antibodies and anti-PD-1 antibodies have gained FDA approval for certain tumors. Here we will discuss the current state of checkpoint inhibitors, biomarker strategies, and management of associated toxicities in glioblastoma.

Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade

“…This systemic and local immunosuppression has contributed to limited improvements in GBM patient outcomes, especially after vaccine or immunotherapy trials (Curry and Lim, 2015). In order to model GSC-mediated immunosuppression and to evaluate therapeutic countermeasures, we used the immunocompetent 005 GSC-derived GBM model, which recapitulates GBM hallmarks (Cheema et al, 2013).…”

“…There are over 10 clinical trials of checkpoint inhibitors for GBM (Preusser et al, 2015b). However, efficacy has been limited, while the combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) caused significant toxicity (Curry and Lim, 2015). …”

Costimulatory checkpoint SLAMF8 is an independent prognosis factor in glioma

“…Immunotherapy is a promising treatment with challenges . We found a costimulatory checkpoint molecule, SLAMF8, was important in clinical, molecular, and biological situations of glioma.…”

“…However, checkpoint blockade has therapeutic benefit only for subsets of glioma . Treatment by checkpoint blockade is often accompanied by inflammation that is responsible for immune‐related side effects such as dermatitis, colitis, inflammatory endocrinopathies, and even fatal cerebral edema . Given the limited regenerative capacity of neuronal tissue, adverse events from CNS inflammation of brain parenchyma are particularly deleterious .…”

Perspectives on investigational drugs and immunotherapies for glioblastoma

“…This study is presently ongoing. Similarly, PD-1/PD-L1 blockade is being examined in single and multicenter trials (e.g., NCT02336165; NCT02359565; NCT02337491; NCT02311582; NCT02529072) 9 .…”