title: Immune checkpoint inhibition and its relationship with hypermutation phenoytype as a potential treatment for Glioblastoma.
abstract: 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.
authors.affiliation: Cure Brain Cancer Foundation Biomarkers and Translational Research, Adult Cancer Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, 2052, Australia. m.sinnadurai@student.unsw.edu.au.
authors.forename: Manohan
authors.identifier: 0000-0003-0735-0030
authors.initials: M
authors.lastname: Sinnadurai
authors.affiliation: Cure Brain Cancer Foundation Biomarkers and Translational Research, Adult Cancer Program, Lowy Cancer Research Centre, University of New South Wales, Sydney, 2052, Australia.
authors.forename: Kerrie L
authors.initials: KL
authors.lastname: McDonald
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D005909:Glioblastoma / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D010641:Phenotype; D019139:Tumor Escape / Q000187:drug effects / Q000276:immunology
chemical_list: D000074322:Antineoplastic Agents, Immunological
keywords: Glioblastoma; Immune checkpoint; Mismatch repair; PD-1; PD-L1