A new study has found that patients with recurrent glioblastoma and a very low tumor mutation burden are more responsive to immunotherapies than similar tumors with an abundance of mutations. These findings, published by Gromeier et al in Nature Communications, could serve as a predictive biomarker to help clinicians target immunotherapies to those tumors most likely to respond. They could also potentially lead to new approaches that create the conditions necessary for immunotherapies to be more effective.
"It's been frustrating that glioblastoma is incurable and we've had limited progress improving survival despite many promising approaches," said senior author David Ashley, MD, PhD, Professor in the Departments of Neurosurgery, Medicine, Pediatrics, and Pathology at Duke University School of Medicine. "We've had some success with several different immunotherapies…, 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."
David Ashley, MD, PhD
Methods and Findings
Dr. Ashley and colleagues performed genomic analyses of recurrent glioblastoma tumors from patients treated at Duke with a poliovirus therapy, as well as others who received checkpoint inhibitors.
In both treatment groups, patients with recurrent glioblastomas whose tumors had few mutations survived longer than the patients with highly mutated tumors. This was only true, however, for patients with recurrent tumors, not for patients with newly diagnosed disease who had not yet received treatment.
"This suggests that chemotherapy, which is the standard of care for newly diagnosed glioblastoma, might be altering the inflammatory response in these tumors," said Dr. Ashley. He added that chemotherapy could be serving an important role as a primer to trigger an evolution of the inflammation process in recurrent tumors.
Dr. Ashley said the finding in glioblastoma could also be relevant to other types of tumors, including kidney and pancreatic cancers, which have similarly shown a correlation between low tumor mutations and improved response to immunotherapies.
Disclosure: For full disclosures of the study authors, visit nature.com.
