Scientists have been racing to establish why some patients respond to cancer immunotherapy while others do not. A recent study has linked metabolites produced by certain bacteria in the gut to improved responses to cancer immunotherapy in patients.
The study, whose findings were published in the journal Cell Reports Medicine, was conducted by a large team led by researchers at the University of Nebraska and Cedars-Sinai, alongside collaborators based at other academic institutions. Ramer-Tait from the University of Nebraska led the research effort.
Previous research has variously linked gut microbiota to improved responses to cancer immunotherapy. However, no study had pinpointed a specific microbe or microbial metabolite linked to immunotherapy response improvements in a specific cancer. The research led by Ramer-Tait was able to identify a particular bacterial strain and its metabolite that triggered enhanced responsiveness to immunotherapy against melanoma.
Their preclinical work found that a bacteria type called Bacteroides uniformis, together with the metabolites it produces, helped to suppress the growth of melanoma tumors.
Their work revealed that this type of bacteria converts tryptophan, an amino acid, into indoles. The indoles had the effect of boosting the immune systems of mice to wage a stronger fight against cancer. This research makes a strong case for developing diet-based and microbiome-focused strategies to increase response rates in cancer patients being treated with immunotherapies.
To establish whether a similar mechanism was at play in humans, the team obtained samples from patients that were undergoing immunotherapy treatment against melanoma. Tests revealed that the patients who exhibited strong responses to immunotherapy also happened to have elevated levels of the specific enzymes which trigger the production of indoles.
The team then modified bacteria to compromise their ability to produce indoles and introduced the bacteria into mice with melanoma. The tumors in those mice continued to grow without being hindered by immune system action, proving that the important element wasn’t just the bacterial strain but rather the metabolites they produced while feeding inside the mice.
This opens the door to developing treatment approaches that leverage microbes or the metabolites those microbes produce in order to boost immune system action against cancer. The research also opens the possibility that this treatment approach could be used in the fight against other forms of cancer, not just melanoma.
As more research and development work is done by various entities, including Calidi Biotherapeutics Inc. (NYSE American: CLDI), to bring to market the next generation of immunotherapies indicated for different cancers, more patients are likely to benefit from these treatments. This would be a marked change from the current reality in which only a small fraction of cancer patients benefits from immunotherapy.
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