Immune checkpoint inhibition and its relationship with hypermutation phenoytype as a potential treatment for Glioblastoma.

Glioblastoma (GBM) is the most common malignant brain tumour in adults. Current prognosis with standard treatment is poor. Immunotherapy is a new paradigm in tumour management. Specifically, recent advances in the field of immune checkpoint molecules have led to dramatic results in many cancers. Inhibition of one particular, programmed cell death-1 (PD-1) has recently been shown to be highly effective in melanoma and non-small cell lung cancer. There has also been recent data to suggest potential benefit in GBM. There also appears to be a relationship between immune checkpoint inhibition and hypermutation, in particular with the mismatch repair process. In this review we look at the current knowledge of immune checkpoint inhibitors with a focus on the PD-1 pathway. We will also review the evidence of PD-1 inhibition in GBM and the role of hypermutation in PD-1 inhibition.