Bacteria in the gut affect cancer immunotherapy
The response to cancer immunotherapy appears to depend on bacteria that come from the gut and migrate to the tumor. An improved understanding of cancer immunotherapy could save many lives, as a recent study shows.
A recent study by the University of Texas Southwestern Medical Center and the University of Chicago found that bacteria from our gut affect the response to cancer immunotherapy. The results of the study were published in the English-language journal "Journal of Experimental Medicine".
Influence of intestinal bacteria on immunotherapy
Could the response to cancer immunotherapy depend on bacteria that come from the gut and migrate to the tumor? The results of the new investigation indicate this precisely. It has been found that intestinal bacteria can penetrate the tumor cells and increase the effectiveness of experimental immunotherapy that targets the so-called CD47 protein.
What role does the gut microbiome play?
The researchers wanted to optimize anti-CD47 therapy and better understand the mechanisms involved. They dealt with the gut microbiome. This is known to affect the ability of the gut to ward off pathogens and the response to cancer immunotherapy.
Bifidobacterium can make tumors responsive to treatment
Using mouse models, the researchers found that an intestinal microbe of the Bifidobacterium type accumulates in tumors and converts anti-CD47 tumors that are unresponsive to treatment into responsive ones. The success of the treatment depends on the type of bacteria that are found in the intestines of the animals.
What was the mechanism behind it?
Finally, the mechanism responsible for this was identified and it was found that the combination of antibodies against CD47 and intestinal bacteria works via the body's STING pathway of innate immunity, which is the body's defense line against infections.
Oral transmission or contact transmission of intestinal bacteria?
The experiment examined mice that were raised in two different facilities and had different bacterial mixtures in their intestines. One group responded to Anti-CD47, but the other did not. However, the second group showed a reaction after being housed in the anti-CD47 mice. This indicates that oral transmission or contact transmission of intestinal bacteria took place between the groups.
Antibiotics prevented response to anti-CD47 therapy
The researchers also found that mice with tumors that normally respond to anti-CD47 treatment do not respond to anti-CD47 therapy if their gut bacteria are killed by antibiotics. In contrast, anti-CD47 treatment has been effective in mice that normally do not respond to treatment when these animals carry bifidobacteria - a type of bacteria that is often found in the gastrointestinal tract of healthy mice and humans.
Bacteria activate tumor-destroying immune cells
According to the study, the bacteria migrate into tumors and activate the STING immune signaling pathway. This triggers the production of immune signaling molecules such as type 1 interferons and activates immune cells that attack and appear to destroy the tumor as soon as the anti-CD47 active ingredient abolishes an existing protective effect.
What prevents successful therapy?
If mice are genetically unable to activate type 1 interferon, they do not respond to the bacterial immunotherapy approach. Similarly, mice that do not have access to the STING signaling path showed no benefit from the combined bacterial immunotherapy approach, which confirms that STING signaling is essential for success.
Summary of results
This study shows that some of the bacteria migrate from the intestine to the tumor and enter the cells or the microenvironment, where the bacteria support the ability of the CD47 blockade and facilitate the attack on the tumor. It was found that this happens via the immune signaling pathway, which is called the stimulator of the interferon genes (STING), the researchers report. The results suggest that a probiotic could be used to improve anti-CD47 therapy.
More research is needed
"It is very likely that more than one type of gut microbiota could similarly increase tumor immunity, and we would like to investigate," study author Professor Yang-Xin Fu of the University of Texas Southwestern added in a press release. (as)
Author and source information
This text corresponds to the requirements of the medical literature, medical guidelines and current studies and has been checked by medical doctors.
- Could cancer immunotherapy success depend on gut bacteria ?, UT Southwestern Medical Center (Published 3/6/2020), UT Southwestern Medical Center
- Yaoyao Shi, Wenxin Zheng, Kaiting Yang, Katharine G. Harris, Kaiyuan Ni et al .: Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling, in Journal of Experimental Medicine (published Mar 6, 2020), JEM