Glioblastoma brain tumors are especially complex and puzzling. These tumors are lethal and they occasionally respond to new immunotherapies after they have grown back. Only 20 percent of the patients live well beyond predicted survival times.
The researchers are trying to understand what causes this effect in order to harness immunotherapies to extend more lives.
The study led by Duke's Preston Robert Tisch Brain Tumor Center is published in the journal Nature Communications.
These findings can help serve as a predictive biomarker to help clinicians target immunotherapies to those tumors most likely to respond. This can also potentially lead to new approaches that create conditions required for the immunotherapies to be more effective.
Senior author David Ashley, M.D., Ph.D., professor in the departments of Neurosurgery, Medicine, Pediatrics and Pathology at Duke University School of Medicine said, "It's been frustrating that glioblastoma is incurable and we've had limited progress improving survival despite many promising approaches. We've had some success with several different immunotherapies, including the poliovirus therapy developed at Duke. And while it's encouraging that a subset of patients who do well when the therapies are used to treat recurrent tumors, about 80% of patients still die."
The researchers performed genomic analyses of recurrent glioblastoma tumors from patients treated with the poliovirus therapy as well as others who received so-called checkpoint inhibitors. The checkpoint inhibitors are a form of therapy that releases the immune system to attack tumors.
In both the treatment groups, patients with recurrent glioblastomas whose tumors had few mutations survived longer than the patients who had more mutations in the tumors. However, this was only the case for patients with recurrent tumors, not for patients with newly diagnosed disease who had not yet received treatment.
Ashley said, "This suggests that chemotherapy, which is the standard of care for newly diagnosed glioblastoma, might be altering the inflammatory response in these tumors." Chemotherapy plays an important role as a primer to trigger an evolution of the inflammation process in recurrent tumors.
The researchers stated that these findings can also be relevant to other types of tumors, including kidney and pancreatic cancers that have similarly shown a correlation between low tumor mutations and improved response to immunotherapies.