News Release
Thursday 4 February 2021
For patients with cancer who do not respond to immunotherapy drugs, the transplantation by adjusting the composition of microorganisms in the gut – known as the intestinal microbiome – by means of feces or feces, can help to leave some of these individuals responding to the immunotherapy drugs, 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 researchers 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 control inhibitor, a type of immunotherapy, responded to the drug after receiving a fecal microbiota transplant from a patient responding to the drug do not have. The results suggest that the insertion of certain fecal microorganisms into the patient’s colon can help the patient respond to medications that improve the immune system’s ability to recognize and kill tumor cells. The findings appear in Science on February 4, 2021.
“In recent years, immunotherapy drugs called PD-1 and PD-L1 inhibitors have benefited many patients with certain cancers, but we need new strategies to help patients whose cancer does not respond,” said co-leader of the study, Giorgio Trinchieri, managing director said. , head of the Laboratory for Integrative Cancer Immunology at NCI’s Center for Cancer Research. “Our study is one of the first to show patients that changing the composition of the intestinal microbiome can improve the response to immunotherapy. The data provide evidence that the intestinal microbiome may be a therapeutic target in cancer. ‘
More research is needed, said dr. Trinchieri added, to identify the specific microorganisms that are critical to overcoming a tumor’s resistance to immunotherapy agents and to investigating the biological mechanisms involved.
Research suggests that communities of bacteria and viruses in the gut 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 begin to respond if they receive certain intestinal microorganisms from mice that respond to the drugs.
Changing the gut microbiome can “reprogram” the microenvironments of tumors that resist immunotherapy drugs, making it more favorable for treatment with this drug, Dr. Trinchieri said.
To test whether fecal transplants are safe and can help cancer patients respond better to immunotherapy, Dr. Trinchieri and his colleagues developed a small one-arm clinical trial for patients with advanced melanoma. The patients’ tumors did not respond to one or more rounds of treatment with the immune system inhibitors pembrolizumab (Keytruda) or nivolumab (Opdivo), administered alone or in combination with other drugs. Immunocontrol inhibitors release a inhibitor that prevents the immune system from attacking tumor cells.
In the study, the fecal transplants, obtained from patients with advanced melanoma who responded to pembrolizumab, were analyzed to ensure that no infectious agents were transmitted. After treatment with saline and other solutions, the fecal transplants were delivered to the colon by patients by colonoscopy, and each patient also received pembrolizumab.
Following these treatments, 6 of the 15 patients who did not initially respond to pembrolizumab or nivolumab responded with tumor reduction or long-term stabilization. One of these patients showed a continuous response after more than two years and is still followed by researchers, while four other patients are still receiving treatment and have not shown any disease progression for more than a year.
The treatment is well tolerated, although some of the patients experience minor side effects associated with pembrolizumab, including fatigue.
The investigators analyzed the intestinal microbiota of all the patients. The six patients whose cancer stabilized or improved showed an increase in numbers of bacteria associated with the activation of immune cells called T cells and responses to immune control inhibitors.
In addition, the researchers observed biological changes in patients who responded to the transplant by analyzing data on proteins and metabolites in the body. For example, the levels of immune system molecules associated with resistance to immunotherapy decreased, and the levels of biomarkers associated with response increased.
Based on the findings of the study, the researchers suggest that larger clinical trials should be performed to confirm the results and to identify biological markers that can ultimately be used to select patients who are likely to benefit most from treatments that the intestinal microbiome altered.
“We expect future studies to identify which groups of bacteria in the gut can convert patients who do not respond to immunotherapy drugs into patients who do respond,” said Amiran Dzutsev, MD, Ph.D., of NCI’s Center for Cancer Research, co-first author of the study. ‘It can come from patients who have responded, or from healthy donors. “If researchers can determine which microorganisms are critical to the response to immunotherapy, it is possible to deliver these organisms directly to patients who need them, without the need for a fecal transplant,” he added.
The clinical trial was conducted in collaboration with Merck, the manufacturer of pembrolizumab.
About the National Cancer Institute (NCI): NCI leads the National Cancer Program and the NIH’s efforts to dramatically reduce the incidence of cancer and improve the lives of cancer patients and their families, by conducting research into prevention and cancer biology, developing new interventions, and training and mentoring new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call the NCI Contact Center, the Cancer Information Service, at 1-800-4-CANCER (1-800-422-6237).
About the National Institutes of Health (NIH):
NIH, the country’s medical research agency, contains 27 institutes and centers and is part of the U.S. Department of Health and Human Services. NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, investigating the causes, treatments, and drugs for common and rare diseases. Visit www.nih.gov for more information on NIH and its programs.
NIH… To turn discovery into health®