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Current status and future perspective of natural killer cell therapy for cancer

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Medical Review 2023年第4期3卷 305-320页

作者： Xiangyu Zhao Minghao Lin Xiaojun Huang Peking University People's Hospital Peking University Institute of HematologyBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationNational Clinical Research Center for Hematologic DiseaseBeijingChina

Natural killer(NK)cells possess innate abilities to effectively eliminate cancer ***,because of difficulties of proliferation and easy to be induced dysfunction in the setting of cancer post NK cell therapy,the curative effect of NK cell infusion has been constrained and not been widely applicable in clinical *** rapid development of biotechnology has promoted the development of NK cell therapy for cancer *** this review,we will provide a comprehensive analysis of the current status and future prospects of NK cell therapy for cancer,focusing on the biological characteristics of NK cells,as well as strategies to enhance their targeting capabilities and overcome tumor immune suppression within the microenvironment.

关键词： natural killer cell therapy hematological malignancies solid tumors CAR-NK cell therapy

Rapid reconstitution of NK1 cells after allogeneic transplantation is associated with a reduced incidence of graft-versus-host disease

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Science China(Life Sciences) 2018年第8期61卷 902-911页

作者： Xingxing Yu Lingling Xu Yingjun Chang Xiaojun Huang Xiangyu Zhao Peking University People's Hospital Peking University Institute of Hematology Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Beijing 100044 China Peking-Tsinghua Center for Life Sciences Beijing 100871 China Yantai Yu Huang Ding Hospital Yantai 264000 China

The balance between immunostimulation and immunoregulation in T cell immunity is achieved by maintaining specific ratios of Thl, Th2, Th3 and Trl cells. Here, we investigate levels of type 1 （IFN-gamma; NK1）, type 2 （IL-13; NK2）, type 3 （TGF-beta; NK3） and regulatory （IL-10; NKr） cytokines in peripheral blood to assess the cytokine profiles of natural killer （NK） cells following human allogeneic hematopoietic stem cell transplantation （allo-HSCT）. NK2 and NK3 cell expansion was observed after aUo-HSCT; levels of NKr ceils reached donor levels at day 15, though levels of NK1 cells were consistently lower than donor levels until day 60 after allo-HSCT. Multivariate analysis showed that a higher level of NK1 cells by day 15 was associated with a lower overall risk of acute graft-versus-host disease （GVHD）（HR 0.157, P=-0.010） as well as II-IV acute GVHD （HR 0.260, P=-0.059）. Furthermore, higher levels of NK1 cells by day 15 were correlated with lower rates of cytomegalovirus （CMV） reactivation （HR 0.040, 0.005-0.348,/9=-0.003）. These results indicate that rapid reconstitution of NK cells, especially NK1 cells, can help prevent the development of GVHD as well as CMV reactivation after allogeneic transplantation.

关键词： NK1 NK2 NK3 NKr GVHD CMV

Modification of donor lymphocyte infusion: how to improve the outcome?

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Science China(Life Sciences) 2019年第9期62卷 1253-1256页

作者： Yu Wang Lanping Xu Chenhua Yan Xiaojun Huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Peking-Tsinghua Center for Life Sciences Beijing 100871China

(HSCT),which has been acknowledged as a curative procedure,relapse of leukemia remains the leading cause of death following transplantation and is a disappointment to transplant *** relapse occurs due to leukemia cell escape from immune-mediated killing (immune escape) by pre-transplantation conditioning and post-transplantation immune *** exhaustion of donor T cells is one of the common causes of relapse,and donor lymphocyte infusions (DLIs) have the potential to reverse this immune *** who are deemed eligible for intensive treatment at this point are offered either DLI or a second *** to the contemporary understanding,DLI results in the same response and survival obtained via a second transplant but with less toxicity (Kharfan- Dabaja et al.,2018).Starting in the mid-1990s,our group along with few others demonstrated the efficacy of DLI,which was initially confirmed by the Hadassah group in Jerusalem in the late *** the first four patients (with both acute and chronic leukemias) treated by us with DLI,the initial success rate was 100%,which encouraged us to pursue this treatment further.

关键词： intensive treatment escape from along with

A vision for the future of allogeneic hematopoietic stem cell transplantation in the next decade

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Science Bulletin 2022年第19期67卷 1921-1924页

作者： Meng Lv Norbert Claude Gorin Xiao-Jun Huang Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Department of Hematology and cell Therapy European Society for Blood and Marrow Transplantation Global CommitteeHôpital Saint-Antoine AP-HPParis Sorbonne UniversityParis 75012France Peking-Tsinghua Center for Life Sciences Beijing 100871China

The whole field of hematological malignancies has experienced a huge breakthrough during the past 40 *** methodological progress in cytogenetics(e.g.,fluorescence in situ hybridization,FISH),immunophenotyping(e.g.,multicolor flow cytometers),and molecular biology(with the discovery of numerous tumor molecular markers by polymerase chain reaction and,more recently,next-generation sequencing)has paved the way for the new concept of detecting and monitoring undetectable minimal residual disease(uMRD)and the engineering of multiple new targeted therapies,such as tyrosine kinase inhibitors and various immunotherapies,including monoclonal antibodies combined or not with antitumor agents,bispecific T-cell-engaging(BiTE)antibodies and chimeric antigen receptor T(CAR-T)cells(Supplementary Text 1 online).

关键词： antibodies monoclonal breakthrough

Reduced β2-GPI is associated with increased platelet aggregation and activation in patients with prolonged isolated thrombocytopenia after allo-HSCT

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Science China(Life Sciences) 2019年第7期62卷 921-929页

作者： Haixia Fu Jingzhong Zhao Lanping Xu Kaiyan Liu Yu Wang Huan Chen Wei Han Jingzhi Wang Fengrong Wang Xiaojun Huang Xiaohui Zhang Peking University People's Hospital Peking University Institute of HematologyBeijing 100044China Beijing Key Laboratory of hematopoietic stem cell transplantation for the Treatment of Hematological Diseases Beijing 100044China Peking University People's Hospital Department of Clinical LaboratoryBeijing 100044China

We aimed to measure platelet function and its relationship with β2-GPI in prolonged isolated thrombocytopenia(PT) after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Fifty-six patients with PT and 60 allo-HSCT recipients without PT(non-PT controls) were *** aggregation and activation,β2-GPI and anti-β2-GPI antibody levels,vWF antigen,and vWF activity were *** effect of β2-GPI on platelet aggregation was also measured ex *** showed that ADP-induced platelet aggregation significantly increased(39%±7.5% vs.23%±8.5%,P=0.032),and the platelet expression of both CD62 p(33.6%±11.6% vs.8.5%±3.5%,P<0.001) and PAC-1(42.4%±7.6% vs.6.8%±2.2%,P<0.001) was significantly higher in patients with PT than in those without *** lower β2-GPI levels(164.2±12 μg m L^-1 vs.234.2±16 μg mL^-1,P<0.001),higher anti-β2-GPI IgG levels(1.78±0.46 U mL^-1 vs.0.94±0.39 U mL^-1,P<0.001),and increased vWF activity(133.06%±30.50% vs.102.17%±25.90%,P<0.001) were observed in patients with PT than in those without *** ADPinduced platelet aggregation(n=116,r^2=-0.5042,P<0.001) and vWF activity(n=116,r^2=-0.2872,P<0.001) were negatively correlated with β2-GPI *** summary,our data suggested that platelet aggregation and activation were significantly higher in patients with PT than in those without PT,which might be associated with reduced β2-GPI *** reduced β2-GPI levels might be due to the existence of anti-β2-GPI IgG.

关键词： β2-GPI hematopoietic stem cell transplantation prolonged isolated thrombocytopenia platelet aggregation platelet activation

Current status and prospects of hematopoietic stem cell transplantation in China

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Chinese Medical Journal 2022年第12期135卷 1394-1403页

作者： Xiaoqi Wang Ruihao Huang Xiaohui Zhang Xi Zhang Medical Center of Hematology Xinqiao HospitalState Key Laboratory of TraumaBurn and Combined InjuryArmy Medical UniversityChongqing 400037China Peking University People’s Hospital&Peking University Institute of Hematology National Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China

hematopoietic stem cell transplantation(HSCT)is a highly effective and unique medical procedure for the treatment of most hematological *** first allogeneic transplantation was performed by *** Thomas in *** then,the field has evolved and expanded *** first successful allogenic HSCT(allo-HSCT)in China was conducted in *** the development of allo-HSCT in China lagged,China has since made considerable contributions to the process of HSCT worldwide,with more than 10,000 HSCTs performed *** particular,haploid HSCT(haplo-HSCT)technology represented in the Beijing Protocol has demonstrated similar efficacy to human leukocyte antigen-matched HSCT and has gradually become the pre-dominant choice for allo-HSCT in ***,the number of haplo-HSCT procedures exceeds 5000 per year,and the Beijing Protocol has been greatly improved by implementing updated individualized strategies for controlling complications,relapse,and infection *** addition,innovative haplo-HSCT technologies developed by different medical transplantation centers,such as Soochow,Zhejiang,Fujian,Chongqing,and Anhui,have emerged,providing inspiration for the refinement of global *** review will focus on the current activity in this field and highlight important trends that are vital in China’s allo-HSCT process,examining the current viewpoint and future directions.

关键词： hematopoietic stem cell transplantation Haploidentical China

Current status of cord blood transplantation in China

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Chinese Medical Journal 2013年第23期126卷 4594-4596页

作者： CHEN Yu-hong LIU Kai-yan Peking University Institute of Hematology People's Hospital BeijingKey Laboratory of Hematopoietic Stem Cell Transplantation Beijing100044 China

In 1988, Gluckman performed the first cord blood transplant for a 5 year old boy with Fanconi anemia using a cord blood unit from the patient＇s unaffected sister,l Patient remains alive and disease free for 24 years. Since then, extensive researches have established the safety and efficacy of umbilical cord blood transplantation （CBT） in both children and adults with a variety of malignant and non-malignant diseases. As of 2011, more than 25 000 CBTs have been performed. Compared with the unrelated bone marrow （UBM） or peripheral blood stem cells （UPBSC）, unrelated cord blood （UCB） has many theoretical and clinical advantages：（1） non-invasive and easy procurement, with little risk to the mother or newborn; （2） expands donor pool for minorities targeted;

关键词： blood transplantation malignant

Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma

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Signal Transduction and Targeted Therapy 2021年第10期6卷 3045-3061页

作者： Jiajun Xie Zifeng Wang Wenjun Fan Youping Liu Fang Liu Xiangbo Wan Meiling Liu Xuan Wang Deshun Zeng Van Wang Bin He Min Yan Zijian Zhang Mengjuan Zhang Zhijie Hou Chunli Wang Zhijie Kang Wenfeng Fang Li Zhang Eric W-F Lam Xiang Guo Jinsong Yan Yixin Zeng Mingyuan Chen Quentin Liu Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangzhouChina Institute of Cancer stem cell Cancer CenterDalian Medical UniversityDalianChina Department of Hematology Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational MedicineLiaoning Medical Center for Hematopoietic Stem Cell TransplantationDalian Key Laboratory of HematologyDiamond Bay Institute of HematologyThe Affiliated Second Hospital of Dalian Medical UniversityDalianChina Department of Radiation Oncology The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Sun Yat-sen Institute of Hematology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina

Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been *** carci noma(NPC)is a distinctive cancer with poor differe ntiatio n and high prevalenee of Epstein-Barr virus(EBV)***,we show that the expressi on of EBV latent protein LMP1 in duces dediffere ntiated and stem-like status with high plasticity through the transcriptional inhibition of ***,LMP1 upregulates STAT5A and recruits HDAC 1/2 to the CEBPA locus to reduce its histone *** inhibition restored CEBPA expression,reversing cellular dedifferentiation and stem-like status in mouse xeno graft *** fin dings provide a novel mecha nistic epigenetic-based in sight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity.

关键词： LMP1 cancer plasticity

Molecular pathogenesis of acute myeloid leukemia: A diversedisease with new perspectives

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Frontiers of Medicine 2010年第4期4卷 356-362页

作者： Felicitas THOL Arnold GANSER Department of Hematology HemostasisOncologyand Stem Cell TransplantationHannover Medical SchoolHannover 30625Germany

Acute myeloid leukemia(AML)is a very heterogeneous neoplasm of the hematopoietic stem *** important achievements in the treatment of AML,the long term survival of patients with the disease remains *** the pathogenesis of AML better is crucial forﬁnding new treatment *** AML development,hematopoietic precursor cells undergo clonal transformation in a multistep process through acquisition of chromosomal rearrangements and/or different gene *** recent years,novel gene mutations have been found in patients with *** mutations can be divided into two important categories,class I mutations that confer a proliferation advantage and class II mutations that inhibit myeloid *** for some of these mutations is now part of the initial diagnostic work-up in newly diagnosed AML *** about the mutation status of speciﬁc genes is useful for risk-stratiﬁcation,minimal residual disease(MRD)monitoring and increasingly also for targeted therapy,especially for patients with cytogenetically normal AML(CN-AML).Besides chromosomal rearrangements and gene mutations,epigenetic regulation of genes–meaning changes in gene expression by mechanisms other than changes in the underlying DNA sequence–also represents an important mechanism of *** article reviews some of the most common mutations in CN-AML and gives a perspective of the translation of these discoveries from bench to bedside.

关键词： acute myeloid leukemia mutations risk stratiﬁcation