粪便微生物群移植可提高抗 PD-1 抑制剂对抗 PD-1 抑制剂耐药的不可切除或转移性实体癌的疗效。
Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.
发表日期：2024 Jul 25
作者：
Yunjae Kim, Gihyeon Kim, Sujeong Kim, Beomki Cho, Sang-Yeob Kim, Eun-Ju Do, Dong-Jun Bae, Seungil Kim, Mi-Na Kweon, Joon Seon Song, Sang Hyoung Park, Sung Wook Hwang, Mi-Na Kim, Yeongmin Kim, Kyungchan Min, Sung-Han Kim, Mark D Adams, Charles Lee, Hansoo Park, Sook Ryun Park
来源：
Cell Host & Microbe
摘要：
肠道微生物组显着影响免疫反应和免疫检查点抑制剂的功效。我们对 13 名抗 PD-1 难治性晚期实体癌患者进行了一项临床试验 (NCT04264975)，将抗程序性死亡 1 (PD-1) 抑制剂与抗 PD-1 应答者的粪便微生物群移植 (FMT) 相结合。 FMT在13名患者中引起了6名患者的持续微生物群变化和临床获益，其中1名部分缓解，5名疾病稳定，实现了7.7%的客观缓解率和46.2%的疾病控制率。临床反应与血液和肿瘤中细胞毒性 T 细胞和免疫细胞因子的增加相关。我们从 FMT 应答者中分离出了 Merdae 普雷沃氏菌，它通过增强细胞毒性 T 细胞浸润来刺激 T 细胞活性并抑制小鼠体内的肿瘤生长。此外，我们发现唾液乳杆菌和普通拟杆菌可能会抑制抗肿瘤免疫。我们的研究结果表明，含有有益微生物群的 FMT 可以克服晚期实体癌（尤其是胃肠癌）对抗 PD-1 抑制剂的耐药性。版权所有 © 2024 Elsevier Inc. 保留所有权利。
The gut microbiome significantly influences immune responses and the efficacy of immune checkpoint inhibitors. We conducted a clinical trial (NCT04264975) combining an anti-programmed death-1 (PD-1) inhibitor with fecal microbiota transplantation (FMT) from anti-PD-1 responder in 13 patients with anti-PD-1-refractory advanced solid cancers. FMT induced sustained microbiota changes and clinical benefits in 6 of 13 patients, with 1 partial response and 5 stable diseases, achieving an objective response rate of 7.7% and a disease control rate of 46.2%. The clinical response correlates with increased cytotoxic T cells and immune cytokines in blood and tumors. We isolated Prevotella merdae Immunoactis from a responder to FMT, which stimulates T cell activity and suppresses tumor growth in mice by enhancing cytotoxic T cell infiltration. Additionally, we found Lactobacillus salivarius and Bacteroides plebeius may inhibit anti-tumor immunity. Our findings suggest that FMT with beneficial microbiota can overcome resistance to anti-PD-1 inhibitors in advanced solid cancers, especially gastrointestinal cancers.Copyright © 2024 Elsevier Inc. All rights reserved.