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Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients
Erez N. Baruch (Tel Aviv University, Sheba Medical Center), Ilan Youngster (Tel Aviv University, Assaf Harofeh Medical Center), Guy Ben‐Betzalel (Sheba Medical Center), Rona Ortenberg (Sheba Medical Center), Adi Lahat (Sheba Medical Center), Lior Haim Katz (Hadassah Medical Center), Katerina Adler (Bar-Ilan University), Daniela Necula (Sheba Medical Center), Stephen Raskin (Tel Aviv University, Sheba Medical Center), Naamah Bloch (Bar-Ilan University), Д. Л. Ротин (Sheba Medical Center), Liat Anafi (Sheba Medical Center), Camila Avivi (Sheba Medical Center), Jenny Melnichenko (Sheba Medical Center), Yael Steinberg‐Silman (Sheba Medical Center), Ronac Mamtani (University of Pennsylvania), Hagit Harati (Sheba Medical Center), Nethanel Asher (Sheba Medical Center), Ronnie Shapira‐Frommer (Sheba Medical Center), Tal Brosh‐Nissimov (Assuta Medical Center), Yael Eshet (Tel Aviv University, Sheba Medical Center), Shira Ben-Simon (Bar-Ilan University), Ziv Oren (Bar-Ilan University), Md Abdul Wadud Khan (The University of Texas MD Anderson Cancer Center), Moran Amit (The University of Texas MD Anderson Cancer Center), Nadim J. Ajami (The University of Texas MD Anderson Cancer Center), Iris Barshack (Tel Aviv University, Sheba Medical Center), Jacob Schachter (Tel Aviv University, Sheba Medical Center), Jennifer Ann Wargo (The University of Texas MD Anderson Cancer Center), Omry Koren (Bar-Ilan University), Gal Markel (Tel Aviv University, Sheba Medical Center), Ben Boursi (Tel Aviv University, Sheba Medical Center)
Résumé : 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.