Current state and future of co-inhibitory immune checkpoints for the treatment of glioblastoma

Abstract

In the interaction between a tumor and the immune system, immune checkpoints play an important role, and in tumor immune escape, co-inhibitory immune checkpoints are important. Immune checkpoint inhibitors (ICIs) can enhance the immune system’s killing effect on tumors. To date, impressive progress has been made in a variety of tumor treatments; PD1/PDL1 and CTLA4 inhibitors have been approved for clinical use in some tumors. However, glioblastoma (GBM) still lacks an effective treatment. Recently, a phase III clinical trial using nivolumab to treat recurrent GBM showed no significant improvement in overall survival compared to bevacizumab. Therefore, the use of immune checkpoints in the treatment of GBM still faces many challenges. First, to clarify the mechanism of action, how different immune checkpoints play roles in tumor escape needs to be determined; which biomarkers predict a benefit from ICIs treatment and the therapeutic implications for GBM based on experiences in other tumors also need to be determined. Second, to optimize combination therapies, how different types of immune checkpoints are selected for combined application and whether combinations with targeted agents or other immunotherapies exhibit increased efficacy need to be addressed. All of these concerns require extensive basic research and clinical trials. In this study, we reviewed existing knowledge with respect to the issues mentioned above and the progress made in treatments, summarized the state of ICIs in preclinical studies and clinical trials involving GBM, and speculated on the therapeutic prospects of ICIs in the treatment of GBM.

Keywords

• immunotherapy
• glioblastoma
• co-inhibitory immune checkpoint
• checkpoint inhibitors
• combination therapy