Gut microbes can spur immune system to attack cancer
A worldwide study has identified gut bacteria that can boost the immune system's ability to fight tumors. The finding should help improve and personalize immunotherapy treatments for cancer.
Immunotherapy is a general term for treatments that increase the body's own ability to tackle disease.
One such treatment uses drugs called immune checkpoint inhibitors.
These block proteins that cancer cells produce and that protect them from attack by immune cells.
However, not all cases of cancer respond to treatment with immune checkpoint inhibitors, and the drugs can also cause severe side effects.
The new Nature Communications study reveals information that should help identify which people are most likely to benefit from treatment with immune checkpoint inhibitors.
The information concerns the molecular mechanisms through which gut bacteria interact with the immune system to influence its ability to fight cancer.
Sanford Burnham Prebys Medical Discovery Institute in La Jolla, CA, led the large international team that worked on the study, which also involved collaboration with three hospitals.
Gut bacteria, immune system, and melanoma
Thomas Gajewski is a professor of cancer immunotherapy at the University of Chicago, IL, and was not involved in the investigation. He describes it as "an important step" toward expanding "the number of people who benefit from immunotherapy."
The investigators identified 11 strains of gut bacteria whose interaction with the immune system helped slow the growth of melanoma tumors in mice.
In addition, they highlighted a signaling pathway called unfolded protein response (UPR) as a major link between the gut bacteria and the antitumor fighting ability of the immune system.
UPR is a cellular process that helps keep protein populations stable and healthy by clearing away those that cell stress has caused to fold incorrectly.
The investigators found that UPR activity was lower in people with melanoma whose cancer responds to immune checkpoint inhibitors.
They suggest that this highlights UPR activity as a potential marker for selecting people with melanoma who are more likely to benefit from immune checkpoint therapy.
"These results," says senior study author Ze'ev Ronai, a professor at Sanford Burnham Prebys, "[...] identify a collection of bacterial strains that could turn on antitumor immunity and biomarkers that could be used to stratify people with melanoma for treatment with select checkpoint inhibitors."
