In a recent study, Anti-PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM, researchers at Johns Hopkins have found in experiments on mice with a form of aggressive brain cancer, that localised chemotherapy delivered directly to the brain rather than given systemically may be the best way to keep the immune system intact and strong when immunotherapy is also part of the treatment.
The researchers say their study results, reported in Science Translational Medicine, could directly affect the design of immunotherapy clinical trials and treatment strategies for people with a deadly form of brain cancer called glioblastoma.
“We understand that our research was done in a mouse model and not in humans, but our evidence is strong that systemic chemotherapy alters the immune system in a way that it never fully recovers,” says Michael Lim, M.D., associate professor of neurosurgery and director of brain tumor immunotherapy at the Johns Hopkins University School of Medicine, and member of the Johns Hopkins Kimmel Cancer Center.
“With aggressive cancers like glioblastoma, it is important that we don’t handicap the defenses we may need to add alternative treatments, such as immunotherapy, to chemotherapy,” he adds.
Glioblastoma is a particularly aggressive form of cancer, with a typical survival time of just over a year after diagnosis. Current treatments include surgical removal of the visible tumor, radiation and chemotherapy. Because the disease is so lethal, even after aggressive standard treatment, neurosurgeons like Lim are looking to add newer immunotherapies that use the body’s own immune system cells to fight the tumor.
However, one challenge to immunotherapy, Lim says, has been the potential toxic effects of systemic therapies that could damage or interfere with the immune system and weaken the chances for success of immunotherapy approaches. With clinical trials being designed to integrate standard of care with immunotherapy, Lim and his team sought to create a way to accurately assess the impact of localized versus systemic chemotherapy on the immune system’s ability to stay healthy, and to see which kind of chemotherapy would actually improve survival time in the test mice.
The researchers say the results of this study suggest that the systemic chemotherapy profoundly weakens the immune system. The researchers showed that the immune system weakening phenomenon isn’t specific to carmustine and happens in multiple types of systemic chemotherapy, such as temozolomide.
The researchers also reversed the treatment protocols, giving the chemotherapy before the immunotherapy to see if that worked better and improved survival. They didn’t notice a difference in survival time whether the immunotherapy was given before or after the brain-specific chemotherapy.