For cancer patients on immunotherapy, harmful gut bacteria may be more important than helpful bacteria

Melanoma patients receiving therapy that helps their immune system kill cancer cells respond differently to treatment depending on the types of microbes in their gut, and new research suggests microorganisms that interfere with therapy have more influence than the beneficial ones.

The results of a collaboration that included researchers from Oregon State University, the National Cancer Institute, the Frederick National Laboratory for Cancer Research and the University of Pittsburgh were published today in natural medicine.

The research is a key step in the fight against several types of cancer, including melanoma, the deadliest form of skin cancer, said Andrey Morgun of the OSU College of Pharmacy.

“Our findings shed new light on the very complicated interplay between the gut microbiome and the immunotherapeutic response in cancer and pave the way for future studies,” he said.

Nationally, melanoma is the fifth most common cancer. About 100,000 new cases of melanoma will be diagnosed in the United States in the coming 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 involves a therapeutic technique called immune checkpoint blockade, often referred to by its initials ICB, which has revolutionized the treatment of melanoma and cancer in general.

ICB therapy relies on inhibitor 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 preventing T cells from killing cancer cells. So when checkpoints are blocked, T cells can kill cancer cells better.

ICB has been a game-changer in cancer treatment, Morgun said, and several studies have shown that patients’ gut microbes play a role in a patient’s response. The human gut microbiome is a complex community of over 10 trillion microbial cells representing approximately 1,000 different bacterial species.

Morgun and colleagues looked at data from several cohorts of melanoma patients receiving a type of CVI known as anti-programmed cell death protein therapy, abbreviated as anti-PD-1 therapy.

Among other methods, they used a computer modeling technique, cross-realm network analysis, invented by Morgun and Natalia Shulzhenko of Oregon State’s Carlson College of Veterinary Medicine, to determine which bacteria were associated with responses better or worse to treatment.

“We established several microbiotypes and some of them were clearly correlated with response to cancer immunotherapy,” Morgun said. “Two microbial signatures – one relatively heavy with Lachnospiraceae species, the other relatively heavy with Streptococcaceae species – were related to favorable and unfavorable clinical response, respectively.”

The results also suggest that approximately one year after the start of treatment, the gut microbiota becomes a dominant factor in response to treatment, and that treatment-impairing microbes appear to play a more important role than treatment-enhancing ones, a- he added.

Amiran Dzutsev and Giorgio Trinchieri of the National Cancer Institute and Hassane Zarour of the University of Pittsburgh are corresponding authors of the study, which was supported by the National Institutes of Health and the National Cancer Institute.

Source of the story:

Material provided by Oregon State University. Original written by Steve Lundeberg. Note: Content may be edited for style and length.

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