Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor,Cell Host & Microbe

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Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2024-07-25 , DOI: 10.1016/j.chom.2024.06.010
Yunjae Kim ₁ , Gihyeon Kim ₂ , Sujeong Kim ₁ , Beomki Cho ₁ , Sang-Yeob Kim ₃ , Eun-Ju Do ₃ , Dong-Jun Bae ₄ , Seungil Kim ₅ , Mi-Na Kweon ₅ , Joon Seon Song ₆ , Sang Hyoung Park ₇ , Sung Wook Hwang ₇ , Mi-Na Kim ₈ , Yeongmin Kim ₁ , Kyungchan Min ₁ , Sung-Han Kim ₉ , Mark D Adams ₁₀ , Charles Lee ₁₀ , Hansoo Park ₂ , Sook Ryun Park ₁₁

Affiliation

Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea.
Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea; Genome and Company, Suwon-si 16229, Gyeonggi-do, Republic of Korea.
Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea.
PrismCDX Co., Ltd., Hwaseong-si 18469, Gyeonggi-do, Republic of Korea.
Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
Department of Infectious Disease, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.

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 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 and 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.

中文翻译：

粪便微生物群移植可提高抗 PD-1 抑制剂对抗 PD-1 抑制剂难治性不可切除或转移性实体癌的疗效

肠道微生物组显着影响免疫反应和免疫检查点抑制剂的疗效。我们在 13 例抗 PD-1 难治性晚期实体癌患者中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 反应者的粪便微生物群移植（FMT）相结合。FMT 诱导 13 例患者中 6 例持续微生物群变化和临床获益，1 例部分缓解，5 例疾病稳定，客观缓解率为 7.7%，疾病控制率为 46.2%。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 反应者中分离出 Immunoactis，FMT 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的肿瘤生长。此外，我们发现并可能抑制抗肿瘤免疫。我们的研究结果表明，具有有益微生物群的 FMT 可以克服晚期实体癌（尤其是胃肠道癌症）对抗 PD-1 抑制剂的耐药性。

更新日期：2024-07-25

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