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Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-βsignaling

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Frontiers of Medicine 2024年第1期18卷 128-146页

作者： Yuanyuan Hao Panpan Chen Shanshan Guo Mengyuan Li Xueli Jin Minghuan Zhang Wenhai Deng Ping Li Wen Lei Aibin Liang wenbin qian Department of Hematology The Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310009China Department of Hematology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhou450003China Key Laboratory of Laboratory Medicine Ministry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhou325000China Department of Hematology Tongji Hospital of Tongji UniversityShanghai200065China

Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells because of the upregulated expression of the inhibitory receptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the CAR T-cells exposed to plasma exosomes from patients with lymphoma. More importantly, single-cell RNA sequencing revealed that CAR T-cells typically showed differentiated phenotypes and regulatory T-cell (Treg) phenotype conversion. By blocking transforming growth factor β (TGF-β)-Smad3 signaling with TGF-β inhibitor LY2109761, the negative effects of TEXs on Treg conversion, terminal differentiation, and immune checkpoint expression were rescued. Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-β inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.

关键词： tumor-derived exosome chimeric antigen receptor T-cell lymphoma TGF-β

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IQGAP3 promotes the progression of glioma as an immune and prognostic marker

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Oncology Research 2024年第4期32卷 659-678页

作者： XIAOFENG GAO JUANJUAN GE XUZHENG GAO NA MEI YANTING SU SHIGANG SHAN wenbin qian JIANGHENG GUAN ZHENWANG ZHANG LONG WANG Hubei Provincial Key Laboratory of Diabetic Cardiovascular Diseases Xianning Medical CollegeHubei University of Science and TechnologyXianning437100China School of Stomatology and Ophthalmology Xianning Medical CollegeHubei University of Science and TechnologyXianning437100China School of Basic Medical Sciences Xianning Medical CollegeHubei University of Science and TechnologyHubei University of Science and TechnologyXianning437100China School of Pharmacy Xianning Medical CollegeHubei University of Science and TechnologyXianning437100China Department of Neurosurgery The General Hospital of Chinese PLA Central Theater CommandWuhan430070China

Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal *** expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well ***:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor *** impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using ***,the cBioPortal database was used to analyze copy number variations and mutation sites of *** validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying ***:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted *** analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related ***,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of ***-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma *** vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma ***:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.

关键词： IQGAP3 Tumor immune infiltration Prognosis Glioma Biomarker

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An Incremental Algorithm to Feature Selection in Decision Systems with the Variation of Feature Set

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Chinese Journal of Electronics 2015年第1期24卷 128-133页

作者： qian wenbin SHU Wenhao YANG Bingru ZHANG Changsheng School of Software Jiangxi Agriculture University School of Computer and Information Technology Beijing Jiaotong University

Feature selection is a challenging problem in pattern recognition and machine learning. In real-life applications, feature set in the decision systems may vary over time. There are few studies on feature selection with the variation of feature set. This paper focuses on this issue, an incremental feature selection algorithm in dynamic decision systems is developed based on dependency function. The incremental algorithm avoids some recomputations, rather than retrain the dynamic decision system as new one to compute the feature subset from scratch. We firstly employ an incremental manner to update the new dependency function, then we incorporate the calculated dependency function into the incremental feature selection algorithm. Compared with the direct(non-incremental) algorithm, the computational efficiency of the proposed algorithm is improved. The experimental results on different data sets from UCI show that the proposed algorithm is effective and efficient.

关键词： Rough sets Feature selection Attribute reduction Incremental algorithm Dynamic data set.

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Preclinical and clinical trials of oncolytic vaccinia virus in cancer immunotherapy:a comprehensive review

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Cancer Biology & Medicine 2023年第9期20卷 646-661页

作者： Mengyuan Li Minghuan Zhang qian Ye Yunhua Liu wenbin qian Department of Hematology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Hangzhou Rong-Gu Biotechnology Limited Company Hangzhou 310056China Department of Pathology&Pathophysiology and Department of Surgical Oncology of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China

Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic *** cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication;however,recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor ***,oncolytic vaccinia virus(OVV)has gained popularity owing to its safety,potential for systemic delivery,and large gene insertion *** review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo,and provides an overview of ongoing clinical trials and combination *** addition,we discuss the potential benefits and drawbacks of OVV as a cancer therapy,and explore different perspectives in this field.

关键词： Oncolytic virotherapy oncolytic vaccinia virus engineered virus arming strategy

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Somatic Mutations Confer Severe Peripheral Neuropathy in POEMS Syndrome-Associated Multicentric Castleman Disease

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Neuroscience Bulletin 2020年第6期36卷 664-666页

作者： Qingqing Lin Juying Wei Jiejing qian Liangshun You wenbin qian Department of Hematology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Institute of Hematology Zhejiang UniversityHangzhou 310003China Malignant Lymphoma Diagnosis and Therapy Center The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Dear Editor,POEMS-associated multicentric Castleman disease(POEMS-MCD)is a subtype of MCD that presents POEMS symptoms(polyneuropathy,organomegaly,endocrinopathy,M protein,and skin changes)as well as the manifestations of *** these symptoms,polyneuropathy is a critical ***,its mechanism remains poorly *** present study presents a case of severe peripheral neuropathy in a POEMSMCD ***-exome sequencing(WES),threedimensional modeling,and protein stability analysis demonstrated that the mutation V49G in PDLIM5 resulted in instability of the protein,which may play a key role in the pathogenesis of peripheral neuropathy in POEMSMCD.

关键词： POEMS neuropathy Castleman

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糖尿病肾病患者开展血糖与糖化血红蛋白、白蛋白/肌酐比值、肾小球滤过率检验的诊断价值探讨

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糖尿病新世界 2024年第12期27卷 53-55,59页

作者：陈慧芳钱文彬陈吉华泰州市中西医结合医院检验科江苏泰州225300

目的探究糖尿病肾病患者开展生化检验的的诊断价值。方法选取2022年4月—2024年3月泰州市中西医结合医院收治的68例疑似糖尿病肾病患者为研究对象,所有患者均进行血糖与糖化血红蛋白、白蛋白/肌酐比值、肾小球滤过率检测,以肾脏活检为... 详细信息

目的探究糖尿病肾病患者开展生化检验的的诊断价值。方法选取2022年4月—2024年3月泰州市中西医结合医院收治的68例疑似糖尿病肾病患者为研究对象,所有患者均进行血糖与糖化血红蛋白、白蛋白/肌酐比值、肾小球滤过率检测,以肾脏活检为金标准,比较不同指标联合方案(A联合方案:血糖与糖化血红蛋白联合白蛋白/肌酐比值;B联合方案:血糖与糖化血红蛋白联合肾小球滤过率;C联合方案:4项指标联合)的诊断效能(准确度、灵敏度、特异度、阳性预测值、阴性预测值)。结果C联合方案诊断出阳性60例,阴性8例。C联合方案诊断的灵敏度、准确度、阴性预测值均高于A联合方案和B联合方案,差异有统计学意义(P均<0.05)。结论血糖与糖化血红蛋白、白蛋白/肌酐比值、肾小球滤过率联合检测可有效检出糖尿病肾病,为后续治疗提供科学依据。

关键词：糖尿病肾病血糖糖化血红蛋白白蛋白/肌酐比值肾小球滤过率

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SwiftTheft: A Time-Efficient Model Extraction Attack Framework Against Cloud-Based Deep Neural Networks

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Chinese Journal of Electronics 2024年第1期33卷 90-100页

作者： wenbin YANG Xueluan GONG Yanjiao CHEN qian WANG Jianshuo DONG School of Cyber Science and Engineering Wuhan University School of Computer Science Wuhan University College of Electrical Engineering Zhejiang University

With the rise of artificial intelligence and cloud computing, machine-learning-as-a-service platforms,such as Google, Amazon, and IBM, have emerged to provide sophisticated tasks for cloud applications. These proprietary models are vulnerable to model extraction attacks due to their commercial value. In this paper, we propose a time-efficient model extraction attack framework called Swift Theft that aims to steal the functionality of cloud-based deep neural network models. We distinguish Swift Theft from the existing works with a novel distribution estimation algorithm and reference model settings, finding the most informative query samples without querying the victim model. The selected query samples can be applied to various cloud models with a one-time selection. We evaluate our proposed method through extensive experiments on three victim models and six datasets, with up to 16 models for each dataset. Compared to the existing attacks, Swift Theft increases agreement(i.e., similarity) by 8% while consuming 98% less selecting time.

关键词： Performance evaluation Cloud computing Analytical models Computational modeling Estimation Artificial neural networks Artificial intelligence

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Heavy flavour physics and CP violation at LHCb:Aten-year review

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Frontiers of physics 2023年第4期18卷 1-69页

作者： Shanzhen Chen Yiming Li wenbin qian Zhihong Shen Yuehong Xie Zhenwei Yang Liming Zhang Yanxi Zhang Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Nuclear Physics and Technology&School of Physics Peking UniversityBeijing 100871China Key Laboratory of Quark and Lepton Physics of Ministry of Education&Institute of Particle Physics Central China Normal UniversityWuhan 430079China Department of Engineering Physics&Center for High Energy Physics Tsinghua UniversityBeijing 100084China

Heavy flavour physics provides excellent opportunities to indirectly search for new physics at very high energy scales and to study hadron properties for deep understanding of the strong *** LHCb experiment has been playing a leading role in the study of heavy flavour physics since the start of the LHC operations about ten years ago,and made a range of high-precision measurements and unexpected discoveries,which may have far-reaching implications on the field of particle *** review highlights a selection of the most influential physics results on CP violation,rare decays,and heavy flavour production and spectroscopy obtained by LHCb using the data collected during the first two operation periods of the *** upgrade plan of LHCb and the physics prospects are also briefly discussed.

关键词： LHCb flavour physics CP vioation

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Optimal model establishment of whole-process management data for CAR-T therapy in China—how should this be done?

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Cellular & Molecular Immunology 2022年第1期19卷 122-124页

作者： Xiaolei Li Hanren Dai Xian Li Ping Li wenbin qian Aibin Liang Weidong Han Department of Bio-Therapeutics the First Medical CentreChinese PLA General HospitalBeijingChina Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityHefeiChina Department of Hematology the Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiangChina Department of Hematology Tongji Hospital of Tongji UniversityShanghaiChina

Chimeric antigen receptor(CAR)T-cell therapy utilizes patients’own T lymphocytes that are engineered to attack cancer cells[1,2,3].With the US Food and Drug Administration(FDA)approval of four CD19-and one BCMA-targeted CAR therapy for B cell malignancies[4,5],CAR T-cell therapy has finally reached the status of a medicinal product.

关键词： CAR lymphocytes utilize

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Analysis of the genomic landscape of primary central nervous system lymphoma using whole-genome sequencing in Chinese patients

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Frontiers of Medicine 2023年第5期17卷 889-906页

作者： Xianggui Yuan Teng Yu Jianzhi Zhao Huawei Jiang Yuanyuan Hao Wen Lei Yun Liang Baizhou Li wenbin qian Department of Hematology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou310009China Department of Pathology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou310009China National Clinical Research Center for Hematologic Diseases the First Affiliated Hospital of Soochow UniversitySuzhou215006China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)the Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou310009China

Primary central nervous system lymphoma(PCNSL)is an uncommon non-Hodgkin’s lymphoma with poor *** study aimed to depict the genetic landscape of Chinese ***-genome sequencing was performed on 68 newly diagnosed Chinese PCNSL samples,whose genomic characteristics and clinicopathologic features were also *** variations were identified in all patients with a mean of 349,which did not significantly influence *** loss occurred in all samples,while gains were detected in 77.9%of the *** high level of copy number variations was significantly associated with poor progression-free survival(PFS)and overall survival(OS).A total of 263 genes mutated in coding regions were identified,including 6 newly discovered genes(ROBO2,KMT2C,CXCR4,MYOM2,BCLAF1,and NRXN3)detected in≥10%of the ***79B mutation was significantly associated with lower PFS,TMSB4X mutation and high expression of TMSB4X protein was associated with lower OS.A prognostic risk scoring system was also established for PCNSL,which included Karnofsky performance status and six mutated genes(BRD4,EBF1,BTG1,CCND3,STAG2,and TMSB4X).Collectively,this study comprehensively reveals the genomic landscape of newly diagnosed Chinese PCNSLs,thereby enriching the present understanding of the genetic mechanisms of PCNSL.

关键词： primary central nervous system lymphoma whole-genome sequencing TMSB4X copy number variation gene utation

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