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-Nissimov; Yael 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

doi:10.1126/science.abb5920

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

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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 language	English (US)
Pages (from-to)	602-609
Number of pages	8
Journal	Science
Volume	371
Issue number	6529
DOIs	https://doi.org/10.1126/science.abb5920
State	Published - Feb 5 2021

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Baruch, E. N., Youngster, I., Ben-Betzalel, G., Ortenberg, R., Lahat, A., Katz, L., Adler, K., Dick-Necula, D., Raskin, S., Bloch, N., Rotin, D., Anafi, L., Avivi, C., Melnichenko, J., Steinberg-Silman, Y., Mamtani, R., Harati, H., Asher, N., Shapira-Frommer, R., ... Boursi, B. (2021). Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science, 371(6529), 602-609. https://doi.org/10.1126/science.abb5920

Baruch, EN, Youngster, I, Ben-Betzalel, G, Ortenberg, R, Lahat, A, Katz, L, Adler, K, Dick-Necula, D, Raskin, S, Bloch, N, Rotin, D, Anafi, L, Avivi, C, Melnichenko, J, Steinberg-Silman, Y, Mamtani, R, Harati, H, Asher, N, Shapira-Frommer, R, Brosh-Nissimov, T, Eshet, Y, Ben-Simon, S, Ziv, O, Khan, MAW, Amit, M, Ajami, NJ, Barshack, I, Schachter, J, Wargo, JA, Koren, O, Markel, G & Boursi, B 2021, 'Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients', Science, vol. 371, no. 6529, pp. 602-609. https://doi.org/10.1126/science.abb5920

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title = "Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients",

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.",

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

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AU - Youngster, Ilan

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AU - Lahat, Adi

AU - Katz, Lior

AU - Adler, Katerina

AU - Dick-Necula, Daniela

AU - Raskin, Stephen

AU - Bloch, Naamah

AU - Rotin, Daniil

AU - Anafi, Liat

AU - Avivi, Camila

AU - Melnichenko, Jenny

AU - Steinberg-Silman, Yael

AU - Mamtani, Ronac

AU - Harati, Hagit

AU - Asher, Nethanel

AU - Shapira-Frommer, Ronnie

AU - Brosh-Nissimov, Tal

AU - Eshet, Yael

AU - Ben-Simon, Shira

AU - Ziv, Oren

AU - Khan, Md Abdul Wadud

AU - Amit, Moran

AU - Ajami, Nadim J.

AU - Barshack, Iris

AU - Schachter, Jacob

AU - Wargo, Jennifer A.

AU - Koren, Omry

AU - Markel, Gal

AU - Boursi, Ben

PY - 2021/2/5

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N2 - 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.

AB - 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.

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Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients

Abstract

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