Specific Gene Mutations predict Success of glioblastoma immunotherapy

Testing for specific gene mutations may help to predict the patients with glioblastoma who will respond to immunotherapy, according to new research. The findings, published in the journal Nature Medicine also suggest a therapeutic target that could lead to improved immunotherapy in these patients.

Glioblastoma, the most common type of brain cancer, still lacks effective treatment. A type of immunotherapy called immune checkpoint inhibitors — which block the interaction between the PD-L1 protein in cancer cells and PD-1 in immune cells, boosting the anti-cancer response — has had success in diverse tumour types, such as Hodgkin’s lymphoma. In contrast, a Phase 3 trial of PD-1 blockers (NCT02017717) showed effectiveness in only 8% of patients with glioblastoma.

Responses to anti-PD1 therapies are linked to the infiltration of immune cells in the tumour microenvironment in various cancer types. The more cells within a tumour and the area surrounding it, the more likely a patient will respond to these treatments. However, glioblastoma is characterized by higher immunosuppression and a low rate of mutations, both of which are associated with poor responses to immune checkpoint inhibitors.