Gut bacteria are to blame for the failure of immune checkpoint therapy for ovarian cancer, our Melanie Rutkowski, PhD, has discovered. Her findings could let us turn the failed treatment into a much-needed lifesaver.
The problem, she found, comes from an unexpected source: the flagella that bacteria use to move. These little propellers are made of material called flagellin, and flagellin, it turns out, cause chaotic cellular communications that prevent the immune cells that are supposed to attack the tumor from finding their way to their targets.
“We found that ovarian tumors enhance the ability of flagellin from the gut to get into the tumor environment, where they normally should not be,” Professor Rutkowski told me. “Because of the gut leakage, immune cells that recognize flagellin become reprogrammed to support tumor growth instead of supporting the killing of tumors during immune therapy.”
Here's the good news: The researchers found that, in early lab tests, they could block the chaotic signaling to restore the effectiveness of immune checkpoint therapy. “In mice whose immune cells that lack the ability to recognize flagellin, immune therapy induced long-term control of ovarian tumor growth in almost 80% of animals,” Professor Rutkowski said. “That we observed this response using multiple aggressive ovarian cancer cell lines suggests that inhibiting this pathway has potential to enhance clinical outcomes for ovarian cancer patients.”
Much more research will need to be done, but it's a promising lead to improve care for a cancer that kills more than 10,000 American women every year.
“The survival outcomes we are achieving in mice that lack the ability to recognize flagellin are extraordinary, especially if we manage to translate these observations into the clinic," Professor Rutkowski said. "I am very hopeful that this work will help to establish a dialogue about the potential that inhibiting the ability of immune cells to recognize bacterial flagellin may have for ovarian cancer patients.”