NIH: Fecal Transplant Boosts Immunotherapy Response in People with Advanced Melanoma

People with metastatic melanoma who are not responding well to treatment with immunotherapy drugs may benefit from the introduction of fecal transplants into their intestines. This is according to a new National Institutes of Health (NIH) study.

Gut Flora

Patients in the study who had advanced melanoma failed to get clinical benefits from treatment with popular immunotherapy drugs. Researchers have observed in recent years that, while this therapy helps many people with cancer, some do not respond.

However, the introduction of fecal microbiota into the patients broke resistance to immunotherapy in some. These people began to respond to drugs that improve the immune system’s capacity to detect and kill tumor cells.

The research was carried out by scientists at the National Cancer Institute (NCI) Center for Cancer Research, a part of the NIH. Researchers from the University of Pittsburgh’s UMPC Hillman Cancer Center also participated.

Findings from the study appeared in the journal Science.

The study

Previously, research had suggested that the composition of the gut microbiome can influence a patient’s response to immunotherapy and chemotherapy.

Dr. Giorgio Trinchieri, a lead researcher in the current study, observed that altering the microorganisms in the gut may, therefore, help to break immunotherapy resistance in cancer patients.

The research team got some people with advanced melanoma that didn’t respond to immunotherapy for a single-arm trial. Specifically, these patients showed resistance to pembrolizumab (Keytruda) and/or nivolumab (Opdivo).

Trinchieri and his team obtained fecal microbiota from advanced melanoma patients who had responded to pembrolizumab. These were assessed to ensure they did not contain harmful agents and then treated with solutions, including saline.

The fecal transplants were then introduced into the colon of resistant patients with the aid of colonoscopy. The patients also got pembrolizumab.

Enhanced immune response

The researchers observed that six of the 15 patients who did not respond to immune checkpoint inhibitors initially began to do so. These exhibited an increase in the numbers of bacteria that help to activate T cells and boost response to immunotherapy.

“Our study is one of the first to demonstrate in patients that the gut microbiome can improve the response to immunotherapy,” said Trinchieri. “The data provide proof of concept that the gut microbiome can be a therapeutic target in cancer.”

The NIH researchers and their collaborators also observed biological changes in patients who responded to the treatment. Molecules in the immune system associated with immunotherapy resistance were reduced, while levels of biomarkers linked to a positive treatment response increased.

There is a need for further research involving a great number of patients, however. The scientists suggest that this was necessary to validate their findings. It will also help to identify patients who are more likely to benefit from this kind of treatment.

The team expressed hope that future studies will make it possible to know particular bacteria that can help break resistance in patients.