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.