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Unveiling gut microbes' influence on cancer patient response to immunotherapy

American Association for the Advancement of Science

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IMAGE: The group performed fecal microbiome transplant (FMT) studies from responding patients on PD-1 blockade (R) or from non-responding patients (NR). In these studies, mice receiving FMT from R had enhanced... view more 

Credit: Dr. Luigi Nezi

Two new studies in cancer patients demonstrate how the composition of gut bacteria can influence response to immunotherapy. Antibiotics, one study showed, render such treatments less effective. And "good bacteria" are more abundant in patients who respond well to immunotherapy, the second study reports. Together, these studies suggest that maintaining healthy gut flora could help combat cancer. First, Bertrand Routy and colleagues explored how antibiotics might influence the outcomes of patients with lung or kidney cancer undergoing immunotherapy with PD-1 inhibitors, a type of therapy that activates the immune system to attack tumors. Patients who had previously taken antibiotics (for urinary or dental infections, for example) had reduced survival compared to those who were not on antibiotics. Analysis of patients' gut microbes revealed that an abundance of the bacterium Akkermansia muciniphila was associated with the best clinical outcome. The species was detectable in 69% and 58% of patients exhibiting a partial response or stable disease respectively, but only detectable in 34% of patients who did not respond to therapy. In mice treated with antibiotics, oral supplementation of the bacteria increased the efficacy of the mice's immune cells, boosting their response to therapy, the authors report.

In the second study, Vancheswaran Gopalakrishnan et al. report that melanoma patients who respond better to the same PD-1 inhibitors have greater gut microbe diversity and abundance of certain bacteria. They collected and analyzed microbiome samples from 112 patients with advanced melanoma who were also taking PD-1 inhibitors. Patients whose microbiomes were enriched with the bacteria Faecalibacterium and Clostridiales were more likely to respond to treatment and to experience longer, progression-free survival, while the opposite was found for patients whose microbiomes were more enriched with Bacteroidales bacteria. Analysis of patients' immune responses revealed that those with the beneficial microbes tended to have more immune cells, which may be more likely to infiltrate and kill tumors. Transplanting the microbes from responding patients into germ-free mice and monitoring their response to PD-1 inhibitors yielded similar results to what was observed in humans, the authors report. Together, the results of the two studies hold important implications for the treatment of cancer patients with immune checkpoint inhibitors.

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