Fecal microbiota transplants correlated with a spike in efficacy for immunotherapy against cancer: study

Eliminating certain bacteria in the gut known to suppress the immune response significantly increases the effectiveness of immunotherapy against cancer, researchers at the University of Montreal Hospital Centre (CHUM) have found.The results are striking: 80% of lung cancer patients responded to treatment, almost double the rates usually observed, and 75% of melanoma patients who received a fecal microbiota transplant responded to treatment, compared to about 60% without a transplant.“We use immunotherapy almost every day with our patients with lung cancer or melanoma, and the gut microbiome is essential for eliciting a response to immunotherapy,” said Dr. Arielle Elkrief, a clinician-researcher at the CHUM Research Centre.“The problem is that 50% of patients will not respond (to immunotherapy).” And we realized in the lab, with mice, that the presence of an intact gut microbiome was essential for the response to immunotherapy.Surprisingly, the researchers discovered that the treatment's success depends not on the presence of beneficial bacteria, but rather on the elimination from the gut of certain bacteria that appear to inhibit the immune response to cancer.Thus, in laboratory trials, the anticancer effect of immunotherapy decreased when these undesirable bacteria were reintroduced into mice.Fecal microbiota transplantation, said Dr. Elkrief, allows for the elimination of these harmful bacteria and strengthens the immune system."Realizing that it's the loss of our own bacteria that makes people respond is truly a completely different way of thinking," added Dr. Rahima Jamal, a hematologist-oncologist at the CHUM (University of Montreal Hospital Centre). “We always think in terms of gains, but here, it’s what we lose . . . that seems to be the key to success.”Another group of researchers has just obtained, and published, very promising results using this same strategy against kidney cancer, noted Dr. Elkrief.Current work, said Dr. Jamal, should help isolate the specific role of fecal transplantation. She and her colleagues hope, in particular, to confirm that transplantation does not increase the toxicity of immunotherapy treatment.“We combine the clinical and laboratory aspects,” she explained. “We try to understand and predict the characteristics of a patient or the transplant that will determine whether someone will respond or whether someone might experience toxicities.”And even though several aspects still need to be explored and clarified, it’s not often in a clinician’s career to see such significant effects, Dr. Jamal emphasized.“It captures the imagination; it’s a game changer that identifies a new way to attack cancer,” she said.Ultimately, a press release explained, this breakthrough “could lead to effective and highly personalized therapies that precisely target the bacteria that interfere with the effectiveness of cancer treatments.”The field of immunotherapy is booming and has been responsible for the most promising breakthroughs in the fight against cancer in the last decade.The human gut microbiome is estimated to be composed of approximately 4,500 different types of bacteria, all of which contribute to the proper functioning of the body. An imbalance in the microbiome can have significant repercussions on health, particularly with regard to digestion, weight, the immune system and mental health.More broadly, the impact of the gut microbiome on multiple aspects of human health is increasingly attracting the attention of the scientific community. Studies published in recent years have demonstrated a potential association between the microbiome and the health of organs such as the heart, brain, and even the eyes.The phase II clinical trial was led by the CRCHUM in collaboration with the London Health Sciences Centre Research Institute and Lawson of St. Joseph’s Health Care London. The findings were published in the journal Nature Medicine.This article has been translated from its original French.

Fecal microbiota transplants correlated with a spike in efficacy for immunotherapy against cancer: study

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