AUTHOR=Lakin Natasha , Rulach Robert , Nowicki Stefan , Kurian Kathreena M. 

TITLE=Current Advances in Checkpoint Inhibitors: Lessons from Non-Central Nervous System Cancers and Potential for Glioblastoma

JOURNAL=Frontiers in Oncology

VOLUME=Volume 7 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2017.00141

DOI=10.3389/fonc.2017.00141

ISSN=2234-943X

ABSTRACT=The adaptive immune system depends on the sequence of antigen presentation, activation, and then inhibition to mount a proportionate response to a threat. Tumours evade the immune response partly by suppressing T-cell activity using immune checkpoints. The use of CTLA-4, PD-1 and PD-L1 antibodies counteract this suppression, thereby enhancing the anti-tumour activity of the immune system. This approach has proven efficacy in melanoma, renal cancer and lung cancer.

There is growing evidence that the central nervous system is accessible to the immune system in the diseased state. Moreover, glioblastomas attract CTLA-4-expressing T-cells and express PD-L1, which inhibit activation and continuation of a cytotoxic T-cell response respectively. This may contribute to the evasion of the host immune response by glioblastoma. Trials are in progress to determine if checkpoint inhibitors will be of benefit in glioblastoma. Radiotherapy could also be helpful in promoting inflammation, enhancing the immunogenicity of tumours, disrupting the blood brain barrier and creating greater antigen release. The combination of radiotherapy and checkpoint inhibitors have been promising in pre-clinical trials, but is yet to show efficacy in humans.

In this review, we summarise the mechanism and current evidence for checkpoint inhibitors in gliomas and other solid tumours, examine the rationale of combining radiotherapy with checkpoint inhibitors and discuss the potential benefits and pitfalls of this approach.