期刊论文详细信息
Frontiers in Immunology
Peripheral blood CD3+HLADR+ cells and associated gut microbiome species predict response and overall survival to immune checkpoint blockade
Immunology
Fabian Beier1  Tim H. Brümmendorf1  Tom Luedde2  Christoph Roderburg2  Sven H. Loosen2  Carsten Bokemeyer3  Joao Gorgulho4 
[1] Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIOABCD), Aachen, Germany;Department of Medicine IV, University Hospital Rheinisch Westfällisch Technische Hochschule (RWTH) Aachen, Aachen, Germany;Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany;Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIOABCD), Aachen, Germany;Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany;Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany;Mildred Scheel Cancer Career Center, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
关键词: PD-1;    HLA-DR;    checkpoint inhibitors;    microbiome;    prognosis;    biomarker;   
DOI  :  10.3389/fimmu.2023.1206953
 received in 2023-04-16, accepted in 2023-08-02,  发布年份 2023
来源: Frontiers
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【 摘 要 】

BackgroundThe search for biomarkers to identify ideal candidates for immune checkpoint inhibitor (ICI) therapy is fundamental. In this study, we analyze peripheral blood CD3+HLADR+ cells (activated T-cells) as a novel biomarker for ICI therapy and how its association to certain gut microbiome species can indicate individual treatment outcomes.MethodsFlow cytometry analysis of peripheral mononuclear blood cells (PBMCs) was performed on n=70 patients undergoing ICI therapy for solid malignancies to quantify HLA-DR on circulating CD3+ cells. 16s-rRNA sequencing of stool samples was performed on n=37 patients to assess relative abundance of gut microbiota.ResultsPatients with a higher frequency of CD3+HLADR+ cells before treatment initiation showed a significantly reduced tumor response and overall survival (OS), a worst response and experienced less toxicities to ICI therapy. As such, patients with a frequency of CD3+HLADR+ cells above an ideal cut-off value of 18.55% had a median OS of only 132 days compared to 569 days for patients below. Patients with increasing CD3+HLADR+ cell counts during therapy had a significantly improved OS. An immune signature score comprising CD3+HLADR+ cells and the neutrophil-lymphocyte ratio (NLR) was highly significant for predicting OS before and during therapy. When allied to the relative abundance of microbiota from the Burkholderiales order and the species Bacteroides vulgatus, two immune-microbial scores revealed a promising predictive and prognostic power.ConclusionWe identify the frequencies and dynamics of CD3+HLADR+ cells as an easily accessible prognostic marker to predict outcome to ICIs, and how these could be associated with immune modulating microbiome species. Two unprecedented immune-microbial scores comprising CD3+HLADR+, NLR and relative abundance of gut bacteria from the Burkhorderiales order or Bacteroides vulgatus species could accurately predict OS to immune checkpoint blockade.

【 授权许可】

Unknown   
Copyright © 2023 Gorgulho, Roderburg, Beier, Bokemeyer, Brümmendorf, Luedde and Loosen

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