Dietary fiber improves outcomes for melanoma patients on immunotherapy – sciencedaily
Melanoma patients receiving treatment that makes it easier for their immune systems to kill cancer cells respond better to treatment when their diets are high in fiber, according to a large international research collaboration that includes the University’s College of Pharmacy of Oregon State.
Posted today in Science, the study conducted by the University of Texas and the National Institutes of Health is a promising development in the fight against several types of cancer, including melanoma, the deadliest form of skin cancer, the researchers said. .
Nationally, melanoma is the fifth most common cancer. About 100,000 new cases of melanoma will be diagnosed in the United States over the next year, and more than 7,000 of those patients are expected to die, according to the American Cancer Society.
One of the most aggressive cancers, melanoma kills by metastasizing or spreading to other organs such as the liver, lungs and brain.
The new study focuses on a therapeutic technique called immune checkpoint blocking, often referred to by its initials ICB, that has revolutionized the treatment of melanoma and cancer in general.
ICB therapy is based on inhibitory drugs that block proteins called checkpoints that are produced by certain cells of the immune system – T cells, for example – and also by certain cancer cells.
Checkpoints help prevent immune responses from being too strong, but sometimes that means T cells aren’t killing cancer cells. So when the checkpoints are blocked, T cells can better kill cancer cells.
“ABI has been a game-changer in the treatment of cancer, and the influence of the gut microbiome on the therapeutic response has been demonstrated in numerous studies, in preclinical models and also in research involving human cohorts,” said Morgun. “A person’s microbiome is shaped by a wide range of environmental factors, including food and drugs, while human genetics account for a much smaller proportion of the variation in the microbiome from person to person.”
The human gut microbiome is a complex community of over 10,000 billion microbial cells from approximately 1,000 different bacterial species. It is still not clear whether dietary fiber intake and the use of commercially available probiotics affect the response to immunotherapy in cancer patients, Morgun said.
Morgun and his collaborators in this study examined hundreds of melanoma patients, analyzing their gut microbiomes, eating habits, probiotic use, disease characteristics, and treatment outcomes. Most of the patients were treated with ICB, usually a type known as anti-programmed cell death protein therapy, abbreviated as anti-PD-1.
A parallel study involving mice implanted with tumors was also part of the research.
In the observational part of the human cohort of the study, a higher intake of dietary fiber was associated with non-progression of the disease in patients on ABI; the most pronounced benefits were seen in patients with a high intake of dietary fiber and without the use of probiotics.
The mouse model generated similar results.
“We have shown that the use of dietary fiber and probiotics, both known to impact the gut microbiome, are associated with different results from BCI,” said Morgun. “From the results of the human cohort, we cannot ascribe causation – there may be other things going on with these patients that we did not measure in this study.”
But Morgun said the results in mice support the idea that anti-tumor immunity is strongest with a diet high in fiber and without probiotics.
To help understand the complexity of the microbiome, Morgun and Natalia Shulzhenko of the Carlson College of Veterinary Medicine at Oregon State invented a computer modeling technique known as transkingdom network analysis.
The model, used in this last work, integrates several types of “omics” data – metagenomics, metabolomics, lipidomics, proteomics, etc. – to determine how interactions between specific types of gut microbes help or hinder the biological functions of the host. In this case, the microbial interactions involved the host’s response to blocking the immune checkpoint.
Importantly, Morgun said, analysis of the transkingdom network in mice showed a family of bacteria, the Ruminococcaceae., among the bodies increased by the high fiber diet; the same bacteria were found in the present study involving humans and in related previous research with people.
Double-blind, randomized dietary intervention studies will be critical in determining whether a targeted and achievable diet change early in treatment with ABI can improve patient outcomes, he said.
“And while the results suggest that some commercially available probiotics may be harmful to patients on ABI, more research is needed to determine which probiotics might actually be of benefit,” Morgun said.
The study was led by Jennifer Wargo, Lorenzo Cohen and Carrie Daniel from the University of Texas and Giorgio Trinchieri from the National Institutes of Health. About 80 scientists participated in the research.
Funders included the NIH and the US State Department.