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High-multiplex single-cell imaging analysis reveals tumor immune contexture associated with clinical outcomes after CAR T-cell therapy

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单位: [1]Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2]Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan 430030, China [3]Department of Hematology, Renmin Hospital of Wuhan University, Wuhan 430060, China [4]Department of Hematology, The First Affiliated Hospital, Harbin Medical University, Harbin 150010, China [5]Department of Hematology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China [6]Department of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [7]Biomedical Research Core Facilities, Westlake University, Hangzhou 310024, China [8]Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan 430030, China [9]Research Institute of Huazhong University of Science and Technology in Shenzhen, Shenzhen 518000, China
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Chimeric antigen receptor (CAR) T-cell therapy has made great progress in treating lymphoma, yet patient outcomes still vary greatly. The lymphoma microenvironment may be an important factor in the efficacy of CAR T therapy. In this study, we designed a highly multiplexed imaging mass cytometry (IMC) panel to simultaneously quantify 31 biomarkers from 13 patients with relapsed/refractory DLBCL who received CAR19/22 T-cell therapy. A total of twenty sections were sampled before CAR T-cell infusion or after infusion when relapse occurred. 35 cell clusters were identified, annotated and subsequently redefined into 10 metaclusters. The CD4+ T-cell fraction was positively associated with remission duration. Significantly higher Ki67, CD57, and TIM3 levels and lower CD69 levels on T cells, especially the CD8+/CD4+ Tem and Te cell subsets, were seen in patients with poor outcomes. Cellular neighborhood containing more immune cells was associated with longer remission. Fibroblasts and vascular endothelial cells resided much closer to tumor cells in patients with poor response and short remission after CAR T therapy. Our work comprehensively and systematically dissects the relationship between cell composition, state, and spatial arrangement in the DLBCL microenvironment and the outcomes of CAR T-cell therapy, which is beneficial to predict CAR T therapy efficacy.Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

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出版当年[2023]版:
大类 | 1 区 医学
小类 | 1 区 生物工程与应用微生物 1 区 遗传学 1 区 医学:研究与实验
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 生物工程与应用微生物 1 区 遗传学 1 区 医学:研究与实验
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第一作者单位: [1]Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2]Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan 430030, China [3]Department of Hematology, Renmin Hospital of Wuhan University, Wuhan 430060, China
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通讯机构: [1]Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [2]Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan 430030, China [8]Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan 430030, China [9]Research Institute of Huazhong University of Science and Technology in Shenzhen, Shenzhen 518000, China
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