Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

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Science  05 Jan 2018:
Vol. 359, Issue 6371, pp. 91-97
DOI: 10.1126/science.aan3706

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  • RE: Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumours
    • Dr Dianne Sika-Paotonu, Associate Dean (Pacific)/Senior Lecturer Pathology & Molecular Medicine, Wellington School of Medicine & Health Sciences, University of Otago, New Zealand

    To the Editor,

    I read with keen interest the article authored by Routy B. et al (1) and entitled: “Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumours.”

    This series of experiments sought to improve understanding of the gut microbial imbalance and maladaptation associated with (1) cancer and (2) concomitant antibiotic use, and explore the potential impact of this dysbiosis on resistance to immune checkpoint inhibition with the PD-1 blockade when used in cancer patients, and mice with established tumours.

    The authors demonstrated that the efficacy of PD-1 blockade in cancer patients and in tumour bearing mice, was reduced in the presence of concomitant antibiotic administration. The bacteria most significantly associated with responders (R) in RCC and NSCLC was A. municiphilia. Importantly, A. municiphilia was also found to be overrepresented in the stool samples of cancer patients at the time of their diagnosis and it was these particular patients that were shown to benefit from PD-1 checkpoint inhibition.

    Experiments involving fecal microbiota transplantation (FMT) derived from cancer patient stool samples and administered to (1) Germ free animals and (2) antibiotic treated mice in SPF conditions, showed that stool samples from clinical responders to treatment (R) conferred sensitivity to PD-1 blockade, while clinical non-responders (NR) produced resistance. Further work supported the overall findings that...

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    Competing Interests: None declared.

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