AUGUST 29, 2018, NEW YORK— Over the past decade Ralph Weichselbaum, co-director of the Ludwig Center at the University of Chicago and Yang Xin Fu, formerly of Ludwig Chicago, have shown that the immune system mediates many of the tumor-destroying effects of radiation. In a study published in advance online on August 28 in Immunity, the researchers and their colleagues report a specific interaction between therapeutic radiation and immune responses that may be exploited to improve cancer treatment.
The researchers focused on how two signaling pathways mediated by the nuclear factor-κB (NF-κB) respond to radiation therapy in opposing ways. The canonical pathway—and an alternative, non-canonical pathway—have become a major focus of research on inflammation, immunity and cancer.
“Inhibiting what is known as the canonical NF-κB family has been shown to increase cancer cell killing in tissue culture and has become an area of investigation to improve cancer radiotherapy,” said Weichselbaum, who is also chairman of radiation oncology at the University of Chicago. “But despite extensive investigation, earlier results from these studies failed to improve the response to radiotherapy in animals or humans.”
In the current study, teams led by Weichselbaum and Fu, who is now a professor of pathology at the University of Texas Southwestern Medical Center, show that disrupting this pathway in a mouse model actually makes radiotherapy less effective, inhibiting rather than enhancing immune responses essential to tumor targeting.
Interfering with the non-canonical NF-κB pathway, on the other hand, improved the effects of radiotherapy by enhancing the immune system’s ability to interact with radiation. The researchers show that targeting this pathway makes tumors in mice more susceptible to radiotherapy.
The findings suggest novel ways to improve treatment by combining radiation and immunotherapies like checkpoint blockade, and the researchers are examining how their findings might best be translated for cancer therapy.
The press release from which this summary is derived can be found here.