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Functional diversification and dynamics of CAR-T cells in patients with B-ALL

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收录情况： ◇ SCIE

作者：
Li Zongcheng[1] * ; Zhao Lei[2,3,4] * ; Zhang Yuanyuan[2,3,4] ; Zhu Li[2,3,4] ; Mu Wei[2,3,4] ; Ge Tong[2,3,4] ; Jin Jin[2,3,4] ; Tan Jiaqi[2,3,4] ; Cheng Jiali[2,3,4] ; Wang Jue[2,3,4] ; Wang Na[2,3,4] ; Zhou Xiaoxi[2,3,4] ; Chen Liting[2,3,4] ; Chang Zhilin[5] ; Liu Chen[5] ; Bian Zhilei[6,7] ; Liu Bing[1,5,8] ; Ye Lilin[9] ; Lan Yu[8] ; Huang Liang[2,3,4] ; Zhou Jianfeng[2,3,4] ;
单位： [1]State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology, Senior Department ofHematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China [2]Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [3]Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan 432826, China [4]National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou 215006, China [5]State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China [6]Department of Hematology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China [7]Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China [8]Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University,Guangzhou 510632, China [9]Institute of Immunology, Third Military Medical University, Chongqing 400038, China
出处：
DOI： 10.1016/j.celrep.2023.113263
ISSN：

摘要：
Understanding of cellular evolution and molecular programs of chimeric antigen receptor-engineered (CAR)-T cells post-infusion is pivotal for developing better treatment strategies. Here, we construct a longitudinal high-precision single-cell transcriptomic landscape of 7,578 CAR-T cells from 26 patients with B cell acute lymphoblastic leukemia (B-ALL) post-infusion. We molecularly identify eight CAR-T cell subtypes, including three cytotoxic subtypes with distinct kinetics and three dual-identity subtypes with non-T cell characteristics. Remarkably, long-term remission is coincident with the dominance of cytotoxic subtypes, while leukemia progression is correlated with the emergence of subtypes with B cell transcriptional profiles, which have dysfunctional features and might predict relapse. We further validate in vitro that the generation of B-featured CAR-T cells is induced by excessive tumor antigen stimulation or suppressed TCR signaling, while it is relieved by exogenous IL-12. Moreover, we define transcriptional hallmarks of CAR-T cell subtypes and reveal their molecular changes along computationally inferred cellular evolution in vivo. Collectively, these results decipher functional diversification and dynamics of peripheral CAR-T cells post-infusion.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

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出版当年[2022]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
最新[2025]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
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出版当年[2021]版：
Q1 CELL BIOLOGY
最新[2023]版：
Q1 CELL BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者单位： [1]State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology, Senior Department ofHematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China
共同第一作者：
通讯作者：
通讯机构： [1]State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology, Senior Department ofHematology, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China [2]Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China [3]Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan 432826, China [4]National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou 215006, China [5]State Key Laboratory of Proteomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China [8]Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University,Guangzhou 510632, China
推荐引用方式(GB/T 7714)：
Li Zongcheng,Zhao Lei,Zhang Yuanyuan,et al.Functional diversification and dynamics of CAR-T cells in patients with B-ALL[J].CELL REPORTS.2023,42(10):doi:10.1016/j.celrep.2023.113263.
APA：
Li Zongcheng,Zhao Lei,Zhang Yuanyuan,Zhu Li,Mu Wei...&Zhou Jianfeng.(2023).Functional diversification and dynamics of CAR-T cells in patients with B-ALL.CELL REPORTS,42,(10)
MLA：
Li Zongcheng,et al."Functional diversification and dynamics of CAR-T cells in patients with B-ALL".CELL REPORTS 42..10(2023)

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