Studying the Pathways That Prevent Self-Defense

This article was originally published in the Northwestern University Feinberg School of Medicine News Center. 

The standard of care for adult patients with glioblastoma includes surgical resection, radiotherapy and chemotherapy. But even with those aggressive treatments, median survival for this fatal and incurable brain cancer is only just over a year. In an effort to improve those rates, Derek Wainwright, PhD, assistant professor of Neurological Surgery at Northwestern University Feinberg School of Medicine, and his team of scientists are studying strategies to reverse pathways that prevent the immune system from fighting glioblastoma.

Wainwright’s research is an example of immunotherapy, a breakthrough approach to treating cancer that aims to use the body’s own immune system to kill cancer cells.

In a recent review, Wainwright, who is also a research scientist at  the Lou and Jean Malnati Brain Tumor Institute of Robert H. Lurie Comprehensive Cancer Center of Northwestern University at Northwestern Memorial Hospital, 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 that can lead to immunosuppression, and overexpression of IDO1 in glioblastoma is associated with decreased overall survival.

“Effective inhibitors of IDO1 are desperately needed to increase the value of therapies that stimulate the immune system for patients with cancer,” Wainwright said. “We’re investigating strategies that include pharmaceutical-grade IDO1 inhibitors. It’s exciting, because this can be immediately translated into the clinic.”

In addition to analyzing immunosuppressive pathways in human glioblastoma, Wainwright’s team works with mouse models to compare the younger and older immune systems.

“The majority of mouse studies use young mice that are between six and 10 weeks old. However, the median age of a glioblastoma patient is 55 years old – equivalent to 72 weeks of age in mice – and 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.”