The Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, Tel-HaShomer, Israel.
Department of Clinical Immunology and Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Science. 2021 Feb 5;371(6529):602-609. doi: 10.1126/science.abb5920. Epub 2020 Dec 10.
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.
肠道微生物组已被证明会影响抗肿瘤 PD-1（程序性细胞死亡蛋白-1）免疫疗法在临床前小鼠模型和观察性患者队列中的反应。然而，在临床试验中尚未研究癌症患者的肠道微生物组的调节。在这项研究中，我们进行了一项 I 期临床试验，以评估粪便微生物群移植（FMT）和重新诱导抗 PD-1 免疫疗法在 10 名抗 PD-1 难治性转移性黑色素瘤患者中的安全性和可行性。我们观察到三名患者有临床反应，包括两名部分缓解和一名完全缓解。值得注意的是，FMT 治疗与肠道固有层和肿瘤微环境中免疫细胞浸润和基因表达谱的有利变化相关。这些早期发现对于调节癌症治疗中的肠道微生物组具有重要意义。
