Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients PMID: 33303685

RQC and Longevity Regulation

2026-09-03

Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients

Science. 2021 Feb 5;371(6529):602-609. doi: 10.1126/science.abb5920.

Erez N Baruch ¹ ² , Ilan Youngster ³ ⁴ , Guy Ben-Betzalel ⁵ , Rona Ortenberg ⁵ , Adi Lahat ⁶ , Lior Katz ⁷ , Katerina Adler ⁸ , Daniela Dick-Necula ⁹ , Stephen Raskin ⁴ ¹⁰ , Naamah Bloch ¹¹ , Daniil Rotin ⁹ , Liat Anafi ⁹ , Camila Avivi ⁹ , Jenny Melnichenko ⁵ , Yael Steinberg-Silman ⁵ , Ronac Mamtani ¹² , Hagit Harati ⁵ , Nethanel Asher ⁵ , Ronnie Shapira-Frommer ⁵ , Tal Brosh-Nissimov ¹³ , Yael Eshet ⁴ ⁹ ¹⁴ , Shira Ben-Simon ¹¹ , Oren Ziv ¹¹ , Md Abdul Wadud Khan ¹⁵ , Moran Amit ¹⁶ , Nadim J Ajami ¹⁵ , Iris Barshack ⁴ ⁹ , Jacob Schachter ⁵ ⁴ , Jennifer A Wargo ¹⁵ ¹⁷ , Omry Koren ¹¹ , Gal Markel ^# ¹ ² ¹⁸ , Ben Boursi ^# ⁴ ¹⁹ ²⁰

Affiliations

1. The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel. [email protected] [email protected].
2. Department of Clinical Immunology and Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
3. Pediatric Division and the Microbiome Research Center, Shamir (Assaf Harofeh) Medical Center, Be'er Ya'akov, Israel.
4. School of Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
5. The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel.
6. Department of Gastroenterology, Sheba Medical Center, Tel HaShomer, Israel.
7. Department of Gastroenterology, Hadassah Medical Center, Jerusalem, Israel.
8. Department of Mathematics, Bar Ilan University, Ramat Gan, Israel.
9. Institute of Pathology, Sheba Medical Center, Tel-HaShomer, Israel.
10. Radiological Institute, Sheba Medical Center, Tel HaShomer, Israel.
11. Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
12. Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, USA.
13. Infectious Diseases Unit, Assuta Ashdod University Hospital, Ashdod, Israel.
14. Department of Nuclear Medicine, Sheba Medical Center, Tel HaShomer, Israel.
15. Program for Innovative Microbiome and Translational Research, Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
16. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
17. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
18. Talpiot Medical Leadership Program, Sheba Medical Center, Tel HaShomer, Israel.
19. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA.
20. Department of Oncology, Sheba Medical Center, Tel HaShomer, Israel.
# Contributed equally.

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.