In a notable preclinical research breakthrough, University of Texas Southwestern Medical Center and University of Chicago-based researchers have uncovered a gut-based bacterium that has the ability to accumulate in tumors and improve the effectiveness of immunotherapy in mice.
The results of this preclinical research, published in the Journal of Experimental Medicine (JEM), offers the possibility that treating cancer patients with Bifidobacteria could potentially boost their response to CD47 immunotherapy, a wide-ranging anti-cancer treatment currently under evaluation for multiple clinical trials.
Research Targeting CD47
A protein expressed on the surface of many cancer cells, it is known that inhibiting this protein can enable the patient’s immune system to attack and destroy the tumor. Hence, researchers are working on antibodies targeting CD47 in a variety of scenarios involving clinical trials. To date, preclinical, mice-based studies have produced mixed results—while some mice seem to respond to anti-CD47 treatment, others do not.
The Current Study
In this recent finding, the team based out of UT Southwestern and University of Chicago found that the response to treatment depends on the type of bacteria living in the animals’ gut. Interestingly, tumor-bearing mice that normally respond to anti-CD47 treatment failed to respond if their gut bacteria were killed off by a cocktail of antibiotics. However, anti-CD47 treatment actually became effective in mice that are usually non-responsive when these animals were supplemented with Bifidobacteria, a type of bacteria that is often found in the intestinal tract of healthy mice and humans. Bifidobacteria has also previously been shown to benefit patients with ulcerative colitis.
An Enhanced Weapon
Interestingly, the Bifidobacteria doesn’t just accumulate in the gut but they also migrate into tumors, where they appear to activate an immune signaling pathway called the stimulation of interferon genes (STING) pathway. This action results in the production of further immune signaling molecules and activation of immune cells. When researchers combine with anti-CD47 treatment, these activated immune cells can attack and destroy the surrounding tumor.
Yang-Xin Fu, MD, PhD, University of Southwestern Medical Center
Ralph R Weichselbaum, MD, co-director, Ludwig Center for Metastasis Research, University of Chicago
Call to Action: This research reveals that a specific member of the gut microbial population can actually enhance the anti-tumor efficacy of anti-CD47 by “colonizing the tumor,” reported Yang-Xin Fu from UTSW. University of Chicago’s Weichselbaum reports, “Our results open a new avenue for clinical investigations into the effects of bacteria within tumors and may help explain why some cancer patients fail to respond to immunotherapy.” TrialSite News will continue to monitor these two researchers’ efforts. Sign up for the daily newsletter to receive updates.