Blocking inflammation makes pancreatic cancer vulnerable to immunotherapy
Medicine doesn’t have a great track record treating pancreatic cancer, with treatments like chemo and immunotherapy not making much headway. In a new mouse study from the Washington University School of Medicine in St. Louis, scientists have found that blocking an inflammatory pathway helps make the cancer vulnerable to these therapies.
Pancreatic cancer is one of the most deadly forms of the disease, often diagnosed after it’s spread to other organs. It has a low five-year average survival rate, largely because conventional treatments like chemotherapy, radiation therapy and immunotherapy aren’t as effective as they are for other cancers.
One of its dirty little tricks is to produce inflammation around the tumors, creating an environment that exhausts T cells that come to fight. That includes T cells that have been supercharged through immunotherapy techniques, rendering this promising treatment ineffective.
The researchers on the new study identified a protein called IRAK4 that drives this inflammation. When they administered an IRAK4 inhibitor to mice with pancreatic cancer, they found that inflammatory signaling was reduced, and as such, the animals’ natural T cells could more easily reach and attack the tumors. It also improved the effectiveness of checkpoint immunotherapy.
The IRAK4 inhibitor increased the survival time of mice, compared with a placebo or chemotherapy alone, and that survival rate increased even further when the inhibitor and the chemo were combined. But the best results came when the inhibitor was combined with immunotherapy – an average of 46 days with the combo, up from 25 days with the inhibitor alone. Some of the combo-treated mice survived as long as 100 days.
While this study was only conducted in mice, the researchers are optimistic that it could be applied to humans. IRAK4 inhibitors are already in clinical trials to treat blood cancers, and the scientists on the new study plan to bring this treatment to clinical trials soon, for pancreatic and gastric cancers.
The research was published in the journal Gastroenterology.