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Microbes and Advanced Melanoma Treatment

In the future, giving specific microbes or entire microbial communities may be part of some cancer treatments! This is because the composition of a person's gut microbiome (the community of bacteria, fungi, and viruses) influences whether a person responds to immunotherapy drugs. This means that the mixture and variety of microbial species living in your intestines may determine whether you respond to cancer immunotherapy drugs. Wow!

One recent study found benefits from fecal microbial transplants (FMT) - that is, transplanting the stool (which contains an entire microbial community of bacteria, fungi, viruses) from a donor who had responded well to immunotherapy drugs to a person with advanced melanoma who had not responded to immunotherapy drugs. In total, 15 persons received stool transplants, and 6 of them had changes to the gut microbiome (becoming more like the donor's gut microbiome) so that the immunotherapy drug now worked against melanoma.

Now studies are needed to identify which specific microbes are the ones that were critical for overcoming a tumor's resistance to immunotherapy drugs.

This is very exciting research because the best treatments for advanced melanoma (metastatic melanoma) are immunotherapy drugs, but it only works for a minority of patients at this point. Microbial manipulation (in this case with fecal transplants) could be a game changer!

Excerpts from Science Daily: Fecal microbiota transplants help patients with advanced melanoma respond to immunotherapy

For patients with cancers that do not respond to immunotherapy drugs, adjusting the composition of microorganisms in the intestines -- known as the gut microbiome -- through the use of stool, or fecal, transplants may help some of these individuals respond to the immunotherapy drugs, a new study suggests. Researchers at the National Cancer Institute (NCI) Center for Cancer Research, part of the National Institutes of Health, conducted the study in collaboration with investigators from UPMC Hillman Cancer Center at the University of Pittsburgh. 

In the study, some patients with advanced melanoma who initially did not respond to treatment with an immune checkpoint inhibitor, a type of immunotherapy, did respond to the drug after receiving a transplant of fecal microbiota from a patient who had responded to the drug. The results suggest that introducing certain fecal microorganisms into a patient's colon may help the patient respond to drugs that enhance the immune system's ability to recognize and kill tumor cells. The findings appeared in Science on February 4, 2021.

"In recent years, immunotherapy drugs called PD-1 and PD-L1 inhibitors have benefited many patients with certain types of cancer, but we need new strategies to help patients whose cancers do not respond," said study co-leader Giorgio Trinchieri, M.D., chief of the Laboratory of Integrative Cancer Immunology in NCI's Center for Cancer Research. "Our study is one of the first to demonstrate in patients that altering the composition of the gut microbiome can improve the response to immunotherapy. The data provide proof of concept that the gut microbiome can be a therapeutic target in cancer."

Research suggests that communities of bacteria and viruses in the intestines can affect the immune system and its response to chemotherapy and immunotherapy. For example, previous studies have shown that tumor-bearing mice that do not respond to immunotherapy drugs can start to respond if they receive certain gut microorganisms from mice that responded to the drugs.

To test whether fecal transplants are safe and may help patients with cancer better respond to immunotherapy, Dr. Trinchieri and his colleagues developed a small, single-arm clinical trial for patients with advanced melanoma. The patients' tumors had not responded to one or more rounds of treatment with the immune checkpoint inhibitors pembrolizumab (Keytruda) or nivolumab (Opdivo), which were administered alone or in combination with other drugs. Immune checkpoint inhibitors release a brake that keeps the immune system from attacking tumor cells.

After these treatments, 6 out of 15 patients who had not originally responded to pembrolizumab or nivolumab responded with either tumor reduction or long-term disease stabilization. One of these patients has exhibited an ongoing partial response after more than two years and is still being followed by researchers, while four other patients are still receiving treatment and have shown no disease progression for over a year.

The investigators analyzed the gut microbiota of all of the patients. The six patients whose cancers had stabilized or improved showed increased numbers of bacteria that have been associated with the activation of immune cells called T cells and with responses to immune checkpoint inhibitors.

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