Opposing functions of gut immunomodulatory metabolites on CAR-T therapy.
一项研究纳入德国三个中心的129例患者,采用鸟枪法宏基因组学和靶向质谱分析发现,CAR-T细胞治疗前短链脂肪酸(尤其是戊酸)水平降低与疾病进展风险增加相关;而吲哚类代谢物(包括吲哚-3-甲醛和吲哚-3-乙酸)及支链脂肪酸异戊酸水平升高与不良结局相关。在人源和小鼠CAR-T细胞模型中的功能验证表明,补充戊酸可增强CAR-T细胞疗效,而吲哚-3-甲醛和异戊酸则损害其疗效。研究揭示了免疫调节代谢物对CAR-T细胞治疗的对立作用,对设计代谢物引导的微生物组治疗策略具有重要意义。
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完整作者
Markus Perl、Severin Guetter、Dhyani Shah、Simon Holzinger、Luisa Becker、Misbah Tariq、Philipp Menauer、Simon Delahais、Gloria Lutzny-Geier、Julian N Scherer、Sascha Göttert、Konstantin Herfeld、Paul Heinrich、Klaus Georg Kreitmeier、Claudia Gebhard、Wolfgang Herr、Marcel P Trefny、Janina Doerr、Saba Sameri、Dennis C Harrer、Kai Ziegler-Martin、Sarah Staudt、Leo Hansmann、Matthias Edinger、Daniel Wolff、Daniela Weber、Elisabeth Meedt、Alexander Denk、Andre Gessner、Ernst Holler、Tobias Wertheimer、Klaus Neuhaus、Tingting Zheng、David M Cordas Dos Santos、Sebastian Theurich、Melanie Schirmer、Karin Kleigrewe、Jonas Schluter、Marcel van den Brink、Michael Schmitt、Markus Feuerer、Christoph Heuser-Loy、Jeremy Baldwin、Luca Gattinoni、Michael Rehli、Michael Hudecek、Camille Bigenwald、Laurence Zitvogel、Marion Subklewe、Viktoria Blumenberg、Maria-Luisa Schubert、Christoph Stein-Thoeringer、Maik Luu、Sebastian Kobold、Matthias A Fante、Erik Thiele Orberg、Hendrik Poeck
作者机构
- Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany; Bavarian Cancer Research Center (BZKF), Regensburg, Germany. Electronic address: markus.perl.ukr@gmail.com.
- Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany; Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany.
- Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany.
- Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Munich, Germany.
- Department of Internal Medicine 5, Hematology and Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
- Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany.
- Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany.
- Division of Hematology and Oncology, Department of Medicine, Freiburg University, Freising, Germany.
- Core Facility Microbiome, ZIEL - Institute for Food & Health, Technische Universität München, Freising, Germany.
- Translational Microbiome Data Integration, School of Life Sciences, Technical University of Munich, Freising, Germany; ZIEL - Institute for Food & Health, Technische Universität München, Freising, Germany.
- Gene Center and Department of Biochemistry, LMU Munich, Munich, Germany.
- Department of Medicine III, Hematology/Oncology, LMU University Hospital and Gene Center, LMU Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, a partnership between the DKFZ and BZKF at the University Hospital of the LMU, Germany.
- Translational Microbiome Data Integration, School of Life Sciences, Technical University of Munich, Freising, Germany; ZIEL - Institute for Food & Health, Technische Universität München, Freising, Germany; Center for Organoid Systems, Technical University Munich, Garching, Germany.
- Bavarian Center for Biomolecular Mass Spectrometry, TUM School of Life Sciences, Technical University Munich, Freising, Germany.
- Department of Microbiology, New York University Grossman School of Medicine, New York, NY, USA; Institute for Systems Genetics, NYU Langone Health Grossman School of Medicine, New York, NY, USA.
- Beckman Research Institute, City of Hope, Duarte, CA, USA.
- Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
- Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany; Department of Internal Medicine III, Haematology and Oncology, University Hospital Bonn, Bonn, Germany.
- Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany; Branch Cellular Immunotherapy, Fraunhofer Institute for Cell Therapy and Immunology (IZI), Würzburg, Germany.
- Gustave Roussy Cancer Campus, Villejuif, France.
- Department of Medicine III, Hematology/Oncology, LMU University Hospital and Gene Center, LMU Munich, Munich, Germany; Laboratory for Translational Cancer Immunology, Gene Center LMU Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany; Bavarian Cancer Research Center (BZKF), Munich, Germany.
- Department of Internal Medicine I, University Hospital Tuebingen, Tuebingen, Germany.
- Division of Clinical Pharmacology, Department of Medicine IV, University Hospital, Ludwig Maximilian University (LMU) of Munich, Munich, Germany; Laboratory for Translational Cancer Immunology, Gene Center LMU Munich, Munich, Germany; Bavarian Cancer Research Center (BZKF), Munich, Germany; German Center for Lung Research (DZL), Partner Site Munich, Munich, Germany.
- Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany; Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.
- Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany; Bavarian Cancer Research Center (BZKF), Regensburg, Germany. Electronic address: erik.orberg@ukr.de.
- Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany; Bavarian Cancer Research Center (BZKF), Regensburg, Germany; Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany. Electronic address: hendrik.poeck@ukr.de.
技术路线
粪便宏基因组与靶向质谱(129例三中心队列)→代谢物与疾病进展关联分析→人及小鼠CAR-T细胞模型功能验证
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不含 2026 年,仅展示最近 5 个完整年度。

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