This is yet another demonstration of the key role of the gut microbiota in the response to immunotherapy in the treatment of cancer. “Our results open a new avenue for clinical investigation of the effects of bacteria in tumors and may help explain why some cancer patients do not respond to immunotherapy,” write these researchers from the University of Texas Southwestern Medical Center here. and the University of Chicago. They demonstrate in the Journal of Experimental Medicine that certain bacteria in the gut microbiota can accumulate in tumors and improve the effectiveness of immunotherapy.
Certain intestinal bacteria can indeed stimulate cancer immunotherapy, French teams recently concluded in the journal Science. Other studies had also shown that patients carrying certain types of bacteria in their intestinal microbiota are “more likely” to respond well to immunotherapy, a treatment of choice for certain cancers which consists of stimulating the immune system to attack cancer cells using specially designed antibodies.
Immune signaling pathways activated by bifidobacteria after their migration into tumors of the gastrointestinal tract
These bacteria that colonize the tumor and help destroy it
Here, the American scientists by identifying, in mice, the specific bacteria that can accumulate in tumors and improve the effectiveness of immunotherapy, suggest that the treatment of cancer patients with bifidobacteria could increase their response to l CD47 immunotherapy, a large-scale anticancer treatment currently being evaluated in several clinical trials.
The CD47 protein, a promising target: CD47 is expressed on the surface of many cancer cells and inhibition of this protein can allow the patient’s immune system to attack and destroy the tumor. Antibodies targeting CD47 are currently being tested as treatments for a wide variety of cancers in several clinical trials. But studies in laboratory mice have so far produced mixed results: some mice appear to respond to anti-CD47 treatment, but others do not.
But it all depends on the intestinal microbiota! Indeed, the research team finds that the response to treatment depends on the type of bacteria living in the intestines of animals. Mice carrying tumors which respond normally to anti-CD47 treatment do not respond if their intestinal bacteria are eliminated via a cocktail of antibiotics. In contrast, anti-CD47 treatment becomes very effective in mice supplemented with bifidobacteria, a type of bacteria often found in the gastrointestinal tract of healthy mice and humans.
Bifidobacteria don’t just build up in the gut; they also migrate into the tumor, where they appear to activate an immune signaling pathway called the interferon gene stimulation pathway (STING). This activation induces the production of new immune signaling molecules and boosts the immune cells which, combined with the anti-CD47 treatment, then become capable of destroying the surrounding tumor.
Thus, a very specific type of bacteria in the intestinal microbiota can improve the anti-tumor efficacy of anti-CD47 by colonizing the tumor. The administration of these bifidobacteria appears to be a new and effective strategy for modulating anti-tumor immunotherapies.
Source: Journal of Experimental Medicine March 06 2020 DOI: 10.1084 / jem.20192282 Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling (Schéma Shi et al., 2020- Rockefeller University Press)
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