Gut Bacteria Composition May Determine Melanoma Patients’ Response to Anti-PD-1 Immunotherapy

Gut Bacteria Composition May Determine Melanoma Patients’ Response to Anti-PD-1 Immunotherapy

The presence of a specific bacteria in the gut of patients with melanoma, as well as a greater diversity of gut bacteria, are associated with a better response to anti-PD-1 immunotherapy.

Understanding this relationship between a patient’s gut bacteria profile and the immune system response could promote new cancer prognosis and treatment strategies.

These findings were presented at the 2017 ASCO-SITC Clinical Immuno-Oncology Symposium, held Feb. 23-25 in Orlando, Fla. The presentation was titled “Association of diversity and composition of the gut microbiome with differential responses to PD-1 based therapy in patients with metastatic melanoma.”

“Evidence from preclinical research had previously indicated a relationship between solid tumors, immune response, and the microbiome. Our study was the first of its type to look at the relationship between the microbiome and immunotherapy response in patients,” Vancheswaran Gopalakrishnan, first author of the study, said in a press release.

Anti-PD-1 drugs such as Keytryda (pembrolizumab) and Opdivo (nivolumab) are used to boost the immune system response against cancer cells. These inhibitors block PD-1 activity, allowing the immune cells to detect and attack the tumors more effectively.

Immune checkpoint inhibitors are commonly used to treat melanoma patients, but that approach is not always effective, and some patients who respond to the treatment have short-lasting responses.

To investigate whether the body’s bacteria composition could impact the response to immunotherapies, researchers at The University of Texas MD Anderson Cancer Center characterized the diversity and composition of gut and oral bacteria samples collected from a total of 228 patients with metastatic melanoma.

Among the 110 patients who were treated with anti-PD-1 therapy, those who responded to anti-PD-1 immunotherapy had higher gut bacteria diversity and larger volumes of a specific type of bacteria – Faecalibacterium – than those who did not respond to treatment.

Looking at the patients’ immune responses, the team found that the presence of these particular bacteria was correlated with increased numbers of infiltrated immune cells within the tumors, indicative of a better anti-tumor response.

Non-responders presented increased numbers of bacteriodales, which comprises five families of environmental bacteria, and a much lower diversity of bacteria than responders. No clear difference in oral bacteria samples between treatment responders and non-responders melanoma patients was reported.

“Our findings point to two potential impacts from additional research — analyzing the diversity and composition of the microbiome to predict response to immunotherapy and modulating the gut microbiome to enhance treatment,” said Jennifer Wargo, MD, senior researcher of the study and co-leader of the Melanoma Moon Shot Program from The University of Texas MD Anderson Cancer Center.

Wargo and colleagues are still conducting preclinical studies to determine the underling mechanism that connects bacteria presence and the immune system response.

In collaboration with the Parker Institute for Cancer Immunotherapy (PICI), they also are designing the first clinical trial, which is expected to launch later this year, where they will test the implications of gut bacteria modulation on cancer patient’s response to immune checkpoint inhibitors.

“The microbiome is highly targetable in a variety of ways,” Gopalakrishnan said, including by diet, fecal trabsplants, antibiotics, or by probiotics to boost the presence of helpful bacteria.

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