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Higher PD-1 expression concurrent with exhausted CD8+ T cells in patients with de novo acute myeloid leukemia 被引量:12
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作者 Jiaxiong Tan Shaohua Chen +9 位作者 Yuhong Lu Danlin Yao Ling Xu Yikai Zhang Lijian Yang Jie Chen Jing Lai Zhi Yu Kanger Zhu Yangqiu Li 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2017年第5期463-470,共8页
Objective: To investigate the association between the T cell inhibitory receptor programmed death 1(PD-1)and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia(AML) and AML in c... Objective: To investigate the association between the T cell inhibitory receptor programmed death 1(PD-1)and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia(AML) and AML in complete remission(CR).Methods:Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3+,CD4+ and CD8+ T cells from peripheral blood samples from 20 newly diagnosed,untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry.Twenty-three healthy individuals served as control.Results:A significantly higher percentage of PD-1+ cells were found for CD3+ T cells in the de novo AML group compared with healthy controls.In addition,an increased level of PD-1+ CD8+ T cells,but not PD-1+ CD4+,was found for CD3+ T cells in the de novo AML and AML-CR samples.A higher percentage of CD244+ CD4+,CD244+ CD8+,CD57+ CD4+ and CD57+ CD8+ T cells was found in CD3+ T cells in samples from those with de novo AML compared with those from healthy controls.Strong increased PD-1+ CD244+ and PD-1+ CD57+ coexpression was found for CD4+ and CD8+ T cells in the de novo AML group compared with healthy controls.Conclusions:We characterized the major T cell defects,including co-expression of PD-1 and CD244,CD57-exhausted T cells in patients with de novo AML,and found a particular influence on CD8+ T cells,suggesting a poor anti-leukemia immune response in these patients. 展开更多
关键词 acute myeloid leukemia pd-1 t cell exhaustion
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初诊急性髓系白血病患者T细胞免疫球蛋白黏液素3和程序性死亡分子1的表达及临床意义 被引量:1
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作者 王艳军 《中国当代医药》 CAS 2023年第11期92-95,共4页
目的探索初诊急性髓系白血病患者T细胞免疫球蛋白黏液素3(Tim-3)和程序性死亡分子1(PD-1)的表达水平及其临床意义。方法回顾性选取2018年7月至2020年4月在聊城市第二人民医院住院及门诊初诊的34例急性髓系白血病患者和20例良性血液病患... 目的探索初诊急性髓系白血病患者T细胞免疫球蛋白黏液素3(Tim-3)和程序性死亡分子1(PD-1)的表达水平及其临床意义。方法回顾性选取2018年7月至2020年4月在聊城市第二人民医院住院及门诊初诊的34例急性髓系白血病患者和20例良性血液病患者作为研究对象,根据不同疾病分为观察组(急性髓系白血病,34例)和对照组(良性血液病,20例)。应用流式细胞术分别检测外周血CD3+T细胞Tim-3和细胞程序性死亡-配体1(PD-L1)的表达水平,以及应用实时荧光定量PCR检测骨髓Tim-3 mRNA和PD-L1 mRNA的相对表达量,并进行对比分析。结果观察组患者的外周血CD3+细胞Tim-3的表达、骨髓Tim-3 mRNA均高于对照组,差异有统计学意义(P<0.001);观察组患者的外周血CD3+细胞PD-L1的表达、骨髓PD-L1 mRNA均高于对照组,差异有统计学意义(P<0.001)。结论初诊急性髓系白血病患者Tim-3和PD-L1表达水平升高,在急性髓系白血病免疫抑制微环境的形成中起到了一定作用。 展开更多
关键词 急性髓系白血病 t细胞免疫球蛋白黏液素3 程序性死亡分子-1 流式细胞术 荧光定量PCR技术
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靶向T细胞免疫治疗急性髓性白血病的策略
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作者 李扬秋 《肿瘤防治研究》 CAS 2024年第4期229-233,共5页
急性髓性白血病(AML)常伴有T细胞免疫功能不全,由于免疫检查点(IC)分子表达上调引起T细胞耗竭是其重要原因之一。利用IC抑制剂治疗AML有一定的临床效果,但患者T细胞耗竭的异质性很大,且还存在其他原因引起的T细胞免疫功能不全,多层面分... 急性髓性白血病(AML)常伴有T细胞免疫功能不全,由于免疫检查点(IC)分子表达上调引起T细胞耗竭是其重要原因之一。利用IC抑制剂治疗AML有一定的临床效果,但患者T细胞耗竭的异质性很大,且还存在其他原因引起的T细胞免疫功能不全,多层面分析区分不同类型的免疫缺陷而采取相应的靶向T细胞免疫治疗才是理想的策略。 展开更多
关键词 急性髓性白血病 t细胞 耗竭 免疫检查点分子 免疫治疗
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PD-1、TIM-3、VISTA在急性髓系白血病患者T细胞上的表达及意义 被引量:8
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作者 葛梦君 徐开林 +10 位作者 许婷 唐亚男 李振宇 闫志凌 孙海英 程海 朱锋 桑威 黄一虹 邱婷婷 李德鹏 《中国实验血液学杂志》 CAS CSCD 北大核心 2020年第3期748-752,共5页
目的:研究多种负性共刺激分子在急性髓系白血病(AML)患者外周血T细胞上的表达及其对预后的影响。方法:收集初治、完全缓解(CR)、未缓解(NR)AML患者外周血标本,采用流式细胞术检测CD4^+和CD8^+T细胞PD-1、VISTA、TIM-3的表达水平,并收集... 目的:研究多种负性共刺激分子在急性髓系白血病(AML)患者外周血T细胞上的表达及其对预后的影响。方法:收集初治、完全缓解(CR)、未缓解(NR)AML患者外周血标本,采用流式细胞术检测CD4^+和CD8^+T细胞PD-1、VISTA、TIM-3的表达水平,并收集患者临床资料进行统计分析。结果:初治AML组患者CD4^+和CD8^+T细胞PD-1、VISTA、TIM-3表达水平均较对照组显著增高(P<0.05),CR组CD4^+和CD8^+T细胞PD-1、TIM-3、VISTA表达水平均较初治组及NR组显著降低(P<0.05);初治AML患者CD4^+和CD8^+T细胞TIM-3表达水平与VISTA表达水平正相关(r=0.85,r=0.73);初治AML患者,首次诱导化疗未缓解组及高危组患者CD4^+T细胞PD-1、VISTA表达水平显著上升(P<0.05),高危组CD8^+T细胞TIM-3表达水平显著上升(P<0.05),CBFβ-MYH11突变阳性组CD8^+T细胞VISTA表达水平显著降低(P<0.05)。结论:PD-1、TIM-3、VISTA在AML外周血T细胞上的表达可能参与AML的免疫逃逸,并可能成为急性髓系白血病患者的治疗靶点。 展开更多
关键词 急性髓系白血病 t细胞 免疫逃逸 免疫靶点抑制剂 pd-1 VIStA tIM-3
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CAR-T和PD-1单克隆抗体在急性髓系白血病治疗中的进展和趋势 被引量:5
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作者 王季石 《中国实验血液学杂志》 CAS CSCD 北大核心 2020年第3期1069-1074,共6页
急性髓系白血病(AML)是一种起源于造血干祖细胞的恶性克隆增殖性血液系统肿瘤。传统化疗可使大部分患者获得完全缓解,但截至目前,仅有异基因造血干细胞移植(allo-HSCT)是可能治愈AML的唯一方式。复发、耐药及移植相关死亡仍然是AML治疗... 急性髓系白血病(AML)是一种起源于造血干祖细胞的恶性克隆增殖性血液系统肿瘤。传统化疗可使大部分患者获得完全缓解,但截至目前,仅有异基因造血干细胞移植(allo-HSCT)是可能治愈AML的唯一方式。复发、耐药及移植相关死亡仍然是AML治疗面临的关键问题。因此,寻找新的治疗方式以改善和提高AML患者的预后在当下显得迫切需要。近年来,新型免疫治疗的出现彻底改变了过去数十年对肿瘤治疗的观念。以嵌合抗原受体T细胞(CAR-T)为代表的细胞免疫治疗和PD-1单克隆抗体为代表的免疫检测点抑制剂在血液系统恶性肿瘤中取得显著的疗效。本文就近几年CAR-T和PD-1单克隆抗体在AML临床治疗中的最新研究进展作一综述。 展开更多
关键词 急性髓系白血病 嵌合抗原受体t细胞 pd-1单克隆抗体
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Elf-1基因在急性髓细胞性白血病中的表达情况 被引量:4
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作者 沈琦 郑海涛 +2 位作者 陈少华 杨力建 李扬秋 《暨南大学学报(自然科学与医学版)》 CAS CSCD 北大核心 2009年第6期581-584,共4页
目的:建立实时定量PCR检测Elf-1基因表达水平的方法,了解急性髓细胞性白血病(AML)患者外周血Elf-1基因表达水平。方法:采用SYBR GreenⅠ荧光定量PCR和相对定量分析法检测33例AML患者:M2型17例、M3型6例、M5型10例和20例健康人外周血的... 目的:建立实时定量PCR检测Elf-1基因表达水平的方法,了解急性髓细胞性白血病(AML)患者外周血Elf-1基因表达水平。方法:采用SYBR GreenⅠ荧光定量PCR和相对定量分析法检测33例AML患者:M2型17例、M3型6例、M5型10例和20例健康人外周血的单核细胞的Elf-1表达情况,以β2微球蛋白基因(β2M)作为内参,采用公式2-ΔCt×100%计算Elf-1基因表达水平。结果:AML组Elf-1表达水平(13.518±19.197)%明显高于健康对照组(2.044±1.321)%(P<0.01),不同AML亚型之间Elf-1的表达水平没有显著性差异(P=0.52),但各亚型AML的Elf-1的表达水平均与健康对照组比较均有显著性差异(P<0.01)。结论:建立SYBR GreenⅠ荧光实时定量PCR分析外周血Elf-1表达水平的方法,检测急性髓细胞性白血病Elf-1基因高表达情况。 展开更多
关键词 Elf-1基因 实时定量PCR 急性髓细胞性白血病(AML) t细胞免疫缺陷 tCRζ链
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儿童急性白血病患者外周血胸苷激酶1水平变化的临床意义 被引量:5
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作者 苌哲宗 余红岚 +1 位作者 费樱 喻云平 《中国医药导报》 CAS 2018年第11期71-73,77,共4页
目的探讨血清胸苷激酶1(TK1)水平变化对不同类型儿童急性白血病(AL)的诊断价值及临床意义。方法选取贵州医科大学附属医院及贵阳市儿童医院2015年10月~2017年9月86例儿童AL患者为研究组,分为急性B细胞型淋巴细胞白血病(B-ALL)组38例,急... 目的探讨血清胸苷激酶1(TK1)水平变化对不同类型儿童急性白血病(AL)的诊断价值及临床意义。方法选取贵州医科大学附属医院及贵阳市儿童医院2015年10月~2017年9月86例儿童AL患者为研究组,分为急性B细胞型淋巴细胞白血病(B-ALL)组38例,急性髓系白血病(AML)组26例和急性T细胞型淋巴细胞白血病(T-ALL)组22例。同时将急性淋巴细胞白血病(ALL)患儿分为标危组21例、中危组19例和高危组20例,另设86例健康体检儿童为对照组。空腹抽取静脉血,检测各组的血清TK1水平。结果 B-ALL组、AML组以及TALL组血清TK1水平均高于对照组,T-ALL组血清TK1水平高于AML组,AML组血清TK1水平高于B-ALL组,差异均有统计学意义(P<0.05)。高危组血清TK1水平高于中危组,中危组TK1水平高于标危组,差异均有统计学意义(P<0.05)。结论检测血清TK1水平对儿童AL的筛查和实验室诊断有重要临床参考价值;血清TK1的水平与ALL患儿的临床危险分级有关,可作为其危险分级的一项参考指标。 展开更多
关键词 急性白血病 急性B细胞型淋巴细胞白血病 急性t细胞型淋巴细胞白血病 急性髓系白血病 胸苷激酶1
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Retrospective study of a cohort of adult patients with hematological malignancies in a tropical area
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作者 Jean-Pierre Droz Laure Bianco +4 位作者 Béatrice Cenciu Ma?a Forgues Florin Santa Jérome Fayette Pierre Couppié 《World Journal of Hematology》 2016年第1期37-50,共14页
AIM: To review the characteristics of hematological malignancies in tropical areas, and to focus on the specific difficulties regarding their management. METHODS: This is a retrospective narrative review of cases of p... AIM: To review the characteristics of hematological malignancies in tropical areas, and to focus on the specific difficulties regarding their management. METHODS: This is a retrospective narrative review of cases of patients with hematological malignancies. All medical files of patients with malignant disease whose treatment was coordinated by the HematoOncology service of the Cayenne Hospital in French Guiana between the 1st of January 2010 and the 31 st of December 2012 were reviewed. Clinical data were extracted from the medical files and included: Demographic data, comorbidities, serological status for human immunodeficiency virus, human T-lymphotropic virus 1(HTLV1), hepatitis B virus and hepatitis C virusinfections, cytology and pathology diagnoses, disease extension, treatment, organization of disease management, and follow-up. The subgroup of patients with hematological malignancies and virus-related malignancies were reviewed. Cases involving patients with Kaposi sarcoma, and information on solid tumor occurrence in virus-infected patients in the whole patient population were included. Since the data were rendered anonymous, no informed consent was obtained from the patients for this retrospective analysis. Data were compiled using EXCEL&#174; software, and the data presentation is descriptive only. The references search was guided by the nature of the data and discussion. RESULTS: In total, the clinical files of 594 patients(pts) were reviewed. Hematological malignancies were observed in 87 patients, and Kaposi sarcoma in 2 patients. In total, 70 patients had a viral infection, and 34 of these also had hematological malignancies. The hematological diagnoses were: Multiple myeloma in 27 pts, lymphoma(L) in 43 pts, myeloproliferative disorders in 17 pts and Kaposi sarcoma in two patients. The spectrum of non-Hodgkin lymphomas(NHL) was: Burkitt L(1 pt), follicular L(5 pts), chronic lymphocytic leukemia(5 pts), high-grade NHL(9 pts), mucosa-associated lymphoid tissue NHL(4 pts), T-cell lymphoma(4 pts), Adult T-cell lymphoma-leukemia(ATL)/lymphoma/leukemia(12 pts); three patients had Hodgkin disease. The spectrum of myeloproliferative diseases was: Chronic myelogenous leukemia(8 pts), thrombocytemia(5 pts) and acute leukemia(4 pts). There were no polycythemia vera, myelosclerosis, and myelodysplastic diseases. This appears to be due to bias in the recruitment process. The most important observations were: The specificity of HTLV1- related ATL malignancies, and the high incidence of virus infections in patients with hematological malignancies. Further, we noted several limitations regarding the treatment and organization of disease management. These were not related to the health care organization, but were due to a lack of board-certified hematooncology specialists, a lack of access to diagnostic tools(e.g., cytogenetic and molecular diagnosis, imaging techniques), the unavailability of radiotherapy, and the physical distance from mainland France. Yet the geography and cultures of the country also contributed to the encountered difficulties. These same limitations are seen in tropical countries with low and intermediate household incomes, but they are amplified by economic, social, and cultural issues. Thus, there is often little access to diagnostic procedures, adequate clinical management, and an unavailability of suitable medical treatments. Programs have been developed to establish centers of excellence, training in pathology diagnosis, and to provide free access to treatment.CONCLUSION: Management of hematological malignancies in tropical areas requires particular skills regarding specific features of these diseases and in terms of the affected populations, as well as solid public health policies. 展开更多
关键词 tropical hematology Multiple myeloma NON-HODGKIN LYMPHOMAS CHRONIC lymphoid leukemia Adult t-cell-lymphoma-leukemia Hodgkin disease CHRONIC myeloid leukemia acute leukemia HUMAN t-lymphotropic VIRUS 1 HUMAN immunodeficiency VIRUS
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PD-L1过表达对CLL-1 CAR-T细胞抗急性髓系白血病作用的影响 被引量:2
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作者 林国强 张彦明 +2 位作者 康立清 俞磊 吴德沛 《中华血液学杂志》 CAS CSCD 北大核心 2020年第10期829-835,共7页
目的:探讨程序性死亡受体配体1(PD-L1)对CLL-1 CAR-T细胞抗急性髓系白血病(AML)作用的影响。方法:通过构建PD-L1表达载体、制备慢病毒、转导、单克隆筛选技术获得稳定表达PD-L1的THP-1单克隆细胞株(THP1-PDL1),然后以前期制备的CLL-1 CA... 目的:探讨程序性死亡受体配体1(PD-L1)对CLL-1 CAR-T细胞抗急性髓系白血病(AML)作用的影响。方法:通过构建PD-L1表达载体、制备慢病毒、转导、单克隆筛选技术获得稳定表达PD-L1的THP-1单克隆细胞株(THP1-PDL1),然后以前期制备的CLL-1 CAR-T细胞为效应细胞,以THP-1、THP1-PDL1单克隆细胞株作为靶细胞,分别通过LDH检测、CBA法、CFSE法评价PD-L1过表达对CLL-1 CAR-T细胞裂解功能、炎性因子释放、细胞增殖等功能的影响。结果:①成功制备了PD-L1慢病毒,并筛选获得了稳定表达PD-L1的THP1-PDL1单克隆细胞株,流式细胞术及PCR验证成功。②PD-L1过表达抑制了CLL-1 CAR-T细胞裂解THP-1细胞的能力;效靶比为10∶1时,CLL-1 CAR-T细胞对THP1-PDL1细胞的杀伤效率明显低于对THP-1细胞的杀伤效率[(15.70±9.90)%对(51.95±2.52)%,P<0.05]。③PD-L1过表达减弱了CLL-1 CAR-T细胞释放细胞因子的能力[与THP1-PDL1细胞共培养时对与THP-1细胞共培养时:IFN-γ(115.66±3.13)pg/ml对(1708.16±26.76)pg/ml,P<0.05;IL-6(17.37±0.72)pg/ml对(124.92±4.26)pg/ml,P<0.05;IL-10(5.69±0.13)pg/ml对(124.12±3.02)pg/ml,P<0.05];同时抑制了CLL-1 CAR-T细胞的增殖能力。结论:成功构建了表达PD-L1的THP1-PDL1单克隆细胞株,同时证实了PD-L1过表达对CLL-1 CAR-T细胞抗AML的不利的影响,为通过PD-1/PD-L1通路调控CLL-1 CAR-T细胞功能提供了一定的理论基础。 展开更多
关键词 白血病 髓系 急性 程序性死亡受体配体1 C型凝集素样分子1(CLL-1) 嵌合抗原受体t细胞
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