Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients

Erez N. Baruch, Ilan Youngster, Guy Ben-Betzalel, Rona Ortenberg, Adi Lahat, Lior Katz, Katerina Adler, Daniela Dick-Necula, Stephen Raskin, Naamah Bloch, Daniil Rotin, Liat Anafi, Camila Avivi, Jenny Melnichenko, Yael Steinberg-Silman, Ronac Mamtani, Hagit Harati, Nethanel Asher, Ronnie Shapira-Frommer, Tal Brosh-NissimovYael Eshet, Shira Ben-Simon, Oren Ziv, Md Abdul Wadud Khan, Moran Amit, Nadim J. Ajami, Iris Barshack, Jacob Schachter, Jennifer A. Wargo, Omry Koren, Gal Markel, Ben Boursi

Research output: Contribution to journalArticlepeer-review

Abstract

The gut microbiome has been shown to influence the response of tumors to anti-PD-1 (programmed cell death-1) immunotherapy in preclinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti-PD-1 immunotherapy in 10 patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. These early findings have implications for modulating the gut microbiota in cancer treatment.

Original languageEnglish
Pages (from-to)602-609
Number of pages8
JournalScience
Volume371
Issue number6529
DOIs
StatePublished - 5 Feb 2021

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