The laboratory of Derek Wainwright, PhD, assistant professor of Neurological Surgery, studies strategies to reverse pathways that inhibit the immune system from fighting glioblastoma, a fatal and incurable type of brain cancer.
“Immunosuppression is a dominant player that inhibits the productivity of an anti-tumor immune response against brain tumors,” Wainwright said.
The standard of care for adult patients with glioblastoma includes surgical resection, radiotherapy and chemotherapy, but even with those aggressive treatments median survival is only just over a year. The goal of Wainwright’s lab is to understand how manipulating immunosuppressive pathways can increase survival when combined with existing therapies.
In a recent review published in Clinical Cancer Research, Wainwright discussed how the enzyme indoleamine 2, 3-dioxygenase 1 (IDO1) could play a critical role in future immunotherapies that target glioblastoma. Found in many types of tumors, the enzyme is part of a pathway known for converting the essential amino acid tryptophan into immunosuppressive catabolites that can also be used to produce energy. Overexpression of IDO1 in glioblastoma is associated with decreased overall survival.
“Effective inhibitors of the IDO1-mediated immuno-evasive pathway are desperately needed to increase the value of immunostimulatory therapies for patients with cancer,” Wainwright said. “We’re investigating combinatorial strategies that include pharmaceutical-grade IDO1 inhibitors. If successful, glioblastoma anti-tumor immunity should reinitiate. It’s exciting, because this modality can be immediately translated into the clinic.”
His research is an example of immunotherapy, a burgeoning approach for treating cancer that aims to stimulate the body’s own immune system to kill cancer cells.
“You must have an intact, functional immune system for these IDO1 inhibitors to have a beneficial impact – this is best exemplified by the lack of therapeutic impact when tested in mice without functioning immune systems,” Wainwright explained.
Wainwright’s lab is also developing mouse models to compare the young and old immune system.
“The majority of mouse studies use young mice that are between six and 10 weeks old, given their wide availability and low-cost. However, with the median age of a glioblastoma patient at 55 years old – equivalent to 72 weeks of age in mice – our predictions on what does and does not work deserve a second look,” Wainwright said. “So far, we have found significant differences between the young and old hosts with brain tumors.”
In addition to working with mouse models, his team analyzes immunosuppressive pathways in human glioblastoma.
Wainwright is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. He joined Feinberg in July 2014 from the University of Chicago after being recruited by Feinberg’s former chair of Neurosurgery, Andrew Parsa, MD, PhD.
“Dr. Parsa provided our neuro-oncology research group with a strong foundation in which patient-resected tumors and peripheral blood are immediately transported to the research laboratories,” Wainwright said. “This and the multiple correlative studies my laboratory is running for immunotherapy-related clinical trials in patients, makes this work fun, exciting and high impact. At the end of the day, this research is meant to help people. If we cannot do that, then we’re not doing our job.”
This research is supported by an American Brain Tumor Association Discovery Grant, National Institute of Health grants NIHF32NS073366, NIHK99NS082381 and NIHR00NS082381, the Zell Scholars Program (part of the Zell Family Foundation’s partnership with the Lurie Cancer Center), the Northwestern Brain Tumor Institute and a Cancer Research Institute postdoctoral fellowship.
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