Specific microbes in digestive tract can boost success for cancer immunotherapy

January 4, 2018, University of Chicago Medical Center
Melanoma in skin biopsy with H&E stain — this case may represent superficial spreading melanoma. Credit: Wikipedia/CC BY-SA 3.0

In the Jan. 5, 2018 issue of Science, researchers from the University of Chicago Medicine show that specific strains of commensal bacteria - the swarms of microorganisms naturally dwelling in the intestines - can improve the response rate to immunotherapy for patients being treated for advanced melanoma.

Although these immune system boosting drugs have revolutionized treatment of certain cancers, only about 35 percent of melanoma who receive them get a significant benefit. In their paper, "The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients," the UChicago researchers demonstrate that several defined , including Bifidobacterium longum, Collinsella aerofaciens and Enterococcus faecium, were much more prevalent in the intestines of the 16 patients who responded to treatment (38 percent) than in the 26 patients (62 percent) who did not.

The presence of these specific bacteria in the intestine appears to enhance T-cell infiltration into the tumor microenvironment and augment T-cell killing of cells, increasing the odds of a vigorous and durable response.

The strong correlation between specific gut bacteria and a clinical response to anti-PD-1 immunotherapy suggests "a causal relationship," said study director Thomas Gajewski, MD, PhD, the AbbVie Foundation Professor of Cancer Immunotherapy at the University. "Specific bacteria clearly contribute to improved anti-tumor immunity in patients. The gut microbiota has a more profound effect than we previously imagined."

The current study follows a November 2015 Science paper from Gajewski's laboratory, one of the first to connect the presence of specific intestinal bacteria to greater potency for immunotherapy. These initial papers showed that the composition of the gut microbiome can influence how well these cancer immunotherapies work in mice.

Although the earlier mouse data was striking, "we knew there were multiple barriers that can decrease the odds that immunotherapy will work," Gajewski said. "We initially thought the microbiome was a minor component. But in our current study, these bacteria were a very strong predictor of who would respond."

The current paper focuses on humans - 42 patients going through treatment for metastatic melanoma. The researchers collected stool samples from each patient prior to treatment. Thirty-eight patients then received an anti-PD-1 drug, so-called "checkpoint inhibitors such as nivolumab or pembrolizumab. Four more patients received a related drug, anti-CTLA4 (ipilimumab).

The researchers focused on eight bacterial species that were more prevalent in patients who did respond to therapy as well as two species that were more abundant in patients who did not respond. Because of bacterial variations, the team used three different methods to determine the genetic sequences of the microbes.

Patients with a higher ratio of the "beneficial" bacteria to "non-beneficial" bacteria all showed a , meaning a reduction in tumor size.

The researchers then ran a smaller experiment in reverse. They collected from three human subjects who responded favorably to treatment, and three who did not respond. They transferred those bacteria into the intestines of germ-free mice. Two weeks later they implanted melanoma cells in the mice.

Two out of three mouse groups given bacteria from human responders had slow-growing tumors and two out of three with fecal material from human non-responders had fast-growing tumors. Mice treated with PD-1-blocking drugs only showed tumor shrinkage if they had microbiota from responding patients.

Two other research teams found similar results but pinpointed different bacteria. A group from the Gustave Roussy Cancer Campus in Villejuif, France, suggested that Akkermansia muciniphila contributed to the antitumor effect of the microbiome. Another team from MD Anderson Cancer Center in Houston, Texas, focused on Faecalibacterium and Clostridiales.

"Our results strongly suggest that the microbiota is a major factor, a gatekeeper for the immune response against a tumor," Gajewski said. "Without microbial support, the immune response just never quite gets going."

"Our results have pushed us in two directions," he added. "We have to start experimenting with probiotics as a way to enhance immunotherapy. We hope to launch a clinical trial using Bifidobacteria in 2018."

They also hope to expand the list of both beneficial and potentially harmful gut bacteria in cancer patients and to identify the mechanisms by which influence the immune system's response to cancer control.

"Our current results," the authors conclude, "open the avenue for integrating commensal microbial composition along with tumor genomes and germline genetics into a multi-parameter model for maximizing the ability to predict which patients are likely to respond to immunotherapies such as anti-PD-1."

Explore further: Bacteria in the gut modulates response to immunotherapy in melanoma

More information: The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients, Science  05 Jan 2018: Vol. 359, Issue 6371, pp. 104-108, DOI: 10.1126/science.aao3290 , http://science.sciencemag.org/content/359/6371/104

Related Stories

Bacteria in the gut modulates response to immunotherapy in melanoma

November 2, 2017
Bacteria that live in the human digestive tract can influence how cancer responds to immunotherapy, opening a new avenue for research to improve treatment, a team led by researchers at The University of Texas MD Anderson ...

Good-guy bacteria may help cancer immunotherapies do their job

October 5, 2017
Individuals with certain types of bacteria in their gut may be more likely to respond well to cancer immunotherapy, researchers at the Harold C. Simmons Comprehensive Cancer Center found in a study of patients with metastatic ...

Gut bacteria associated with cancer immunotherapy response in melanoma

February 21, 2017
Melanoma patients' response to a major form of immunotherapy is associated with the diversity and makeup of trillions of potential allies and enemies found in the digestive tract, researchers at The University of Texas MD ...

Gut microbes linked to immunotherapy response in melanoma patients

November 7, 2016
Patients with malignant melanoma - whose disease has spread - are more likely to respond to immunotherapy treatment if they had greater diversity in their gut bacteria, according to new research presented at the National ...

Gut bacteria can dramatically amplify cancer immunotherapy

November 5, 2015
By introducing a particular strain of bacteria into the digestive tracts of mice with melanoma, researchers at the University of Chicago were able to boost the ability of the animal's immune systems to attack tumor cells. ...

Immunotherapy combination safe and 62 percent effective in metastatic melanoma patients

September 7, 2017
Immunotherapy is a promising approach in the treatment of metastatic melanoma, an aggressive and deadly form of skin cancer; but for most patients, immunotherapy drugs so far have failed to live up to their promise and provide ...

Recommended for you

Healthy diets linked to better outcomes in colorectal cancer

October 20, 2018
Colorectal cancer patients who followed healthy diets had a lower risk of death from colorectal cancer and all causes, even those who improved their diets after being diagnosed, according to a new American Cancer Society ...

Why some cancers affect only young women

October 19, 2018
Among several forms of pancreatic cancer, one of them specifically affects women, often young. How is this possible, even though the pancreas is an organ with little exposure to sex hormones? This pancreatic cancer, known ...

Scientists to improve cancer treatment effectiveness

October 19, 2018
Together with researchers from the University of Nantes and the University of Reims Champagne-Ardenne in France, experts from the National Research Nuclear University MEPhI have recently developed a quantum dot-based microarray ...

Mutant cells colonize our tissues over our lifetime

October 18, 2018
By the time we reach middle age, more than half of the oesophagus in healthy people has been taken over by cells carrying mutations in cancer genes, scientists have uncovered. By studying normal oesophagus tissue, scientists ...

Study involving hundreds of patient samples may reveal new treatment options of leukemia

October 17, 2018
After more than five years and 672 patient samples, an OHSU research team has published the largest cancer dataset of its kind for a form of leukemia. The study, "Functional Genomic Landscape of Acute Myeloid Leukemia", published ...

A 150-year-old drug might improve radiation therapy for cancer

October 17, 2018
A drug first identified 150 years ago and used as a smooth-muscle relaxant might make tumors more sensitive to radiation therapy, according to a recent study led by researchers at The Ohio State University Comprehensive Cancer ...

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Doc56
not rated yet Jan 06, 2018
It would be no surprise that the microbiome has an impact on treatment given the gut bacteria are 80% of your immune system. I wonder if the exponential growth of antibiotic usage , killing off all our good bacteria, has anything to do with the similar growth in the cancer rates. Cancer is a weed in the garden. The question is why is the soil allowing the weeds to grow out of control. In this case we are amending the soil with good bacteria and it is helping to fight the weeds. Not rocket sicience.
gzurbay
not rated yet Jan 08, 2018
Interesting paper, - I would suggest this is 1/2 the consideration. All metabolites produced will have status in the mix. In some cases a metabolite may be nutritionally important, neutral, antibiotic, or toxic in immediate or chronic effect. Nerve toxins - food poisoning, eliminating bacteria which suppress disease producing bacteria and their elements including inflammation producing attributes also will weigh in on micro biome health. Epigenetic changes likely contribute in many directions.

We should examine the use of ammonia in ground beef, - it's use to kill contaminants could also suppress beneficial organisms in the gut - depending on ammonia levels retained. In the case of a simple sugar there seems to be potential for a far reaching effect on the micro biome and health see the post:
https://medicalxp...ics.html

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.