Glioblastoma brain tumors are particularly anxious. Inevitably fatal, the tumors occasionally respond to new immunotherapies after they grow back, allowing up to 20% of patients to survive well beyond the survival times. is expected.
What is causing this effect has long been the pursuit of researchers hoping to make use of immunotherapies to further extend life.
New insights from a team led by Duke’s Robert Tisch Preston Brain Tumor Center include Katherine Peters, MD, PhD, Dina Randazzo, DO, and Annick Desjardins, MD at the Department of Neurology. The team found that recurrent glioblastoma tumors with very few tumors are far more vulnerable to immunotherapies than tumors resembling an abundance of mutations.
The result, appearing online Jan. 13 in the magazine Nature Communications, that could be a predictive biomarker to help clinicians target immunotherapies at those tumors most likely to respond. It could also lead to new approaches that create the conditions necessary for immunotherapies to be more effective.
“It has been unfortunate that glioblastoma is not accessible and we have made little progress in improving survival despite many promising approaches,” said lead author David Ashley, MD, PhD, a professor at the departments of Non-Surgery, Medicine, Pediatrics and Pathology at Duke University School of Medicine.
“We have been very successful with a number of different immunotherapies, including the Duke developed poliovirus therapy,” said Ashley. “And while it is encouraging that there is a subset of patients who are doing well when the treatments are used to treat recurrent tumors, around 80% of patients still to die. ”
Ashley and colleagues performed genomic analyzes of recurrent glioblastoma tumors from patients treated at Duke with the poliovirus therapy as well as others who received so-called check-in immunosuppressants, a type of treatment that releasing the immune system to attack tumors.
In all treatment groups, patients with recurrent glioblastomas who had few mutations at the tumors survived longer than patients with highly mutated tumors. This was only true, however, for patients with recurrent tumors, not for patients with neonatal disease who have not yet received treatment.
“This suggests that chemotherapy, which is the standard of care for neonatal glioblastoma, may alter the inflammatory response in these tumors,” said Ashley, noting that chemotherapy could play an important role as a primer to stimulate the evolution of inflammation. process in recurrent tumors.
Ashley said the finding in glioblastoma may also be related to other types of tumors, including renal and pancreatic cancers, which have similarly shown a correlation between low tumor mutations and a better response to immunotherapies.
In addition to Ashley, study authors include Matthias Gromeier, Michael C. Brown, Gao Zhang, Xiang Lin, Yeqing Chen, Zhi Wei, Nike Beaubier, Hai Yan, Yiping He, Annick Desjardins, James E. Herndon II, Frederick S. Varn, Roel G. Verhaak, Junfei Zhao, Dani P. Bolognesi, Allan H. Friedman, Henry S. Friedman, Frances McSherry, Andrea M. Muscat, Eric S. Lipp, Smita K. Nair, Mustafa Khasraw , Katherine B. Peters, Dina Randazzo, John H. Sampson, Roger E. McLendon and Darell D. Bigner.
The study was supported by Brain Tumor Research Charity, Jewish General Fund, Circle of Service Foundation, Uncle Kory Foundation, Department of Defense (W81XWH-16-1-0354) and National Institutes of Health (R35CA197264, P01CA154291, P50CA190991, R01NS108773, R01NS09946, R01NS09946). , R21NS112899, P01CA225622, F32CA224593). Support was also received through the Angels Among Us fundraising event and a gift from the Asness Family.
The authors Gromeier, Brown, Desjardins, Bolognesi, Henry Friedman, Nair, Sampson, Bigner and Ashley have intellectual property associated with the poliovirus therapy, which was licensed to Istari Oncology, Inc. Gromeier, Desjardins, Bolognesi, Allan Friedman, Henry Friedman and Bigner hold equity at Istari Oncology, Inc. Additional disclosures are provided in the published study.
This story originally appeared on The Duke Health website. See it in its original place here.