• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

异质性自然杀伤细胞对急性白血病反应的遗传和分子基础

Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute Leukemia.

作者信息

Makanga Dhon Roméo, Da Rin de Lorenzo Francesca, David Gaëlle, Willem Catherine, Dubreuil Léa, Legrand Nolwenn, Guillaume Thierry, Peterlin Pierre, Lebourgeois Amandine, Béné Marie Christine, Garnier Alice, Chevallier Patrice, Gendzekhadze Ketevan, Cesbron Anne, Gagne Katia, Clemenceau Béatrice, Retière Christelle

机构信息

Etablissement Français du Sang, 44011 Nantes, France.

Université de Nantes, INSERM U1232 CNRS, CRCINA, F-44000 Nantes, France.

出版信息

Cancers (Basel). 2020 Jul 16;12(7):1927. doi: 10.3390/cancers12071927.

DOI:10.3390/cancers12071927
PMID:32708751
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7409189/
Abstract

Natural killer (NK) cells are key cytotoxic effectors against malignant cells. Polygenic and polymorphic Killer cell Immunoglobulin-like Receptor (KIR) and HLA genes participate in the structural and functional formation of the NK cell repertoire. In this study, we extensively investigated the anti-leukemic potential of NK cell subsets, taking into account these genetic parameters and cytomegalovirus (CMV) status. Hierarchical clustering analysis of NK cell subsets based on NKG2A, KIR, CD57 and NKG2C markers from 68 blood donors identified donor clusters characterized by a specific phenotypic NK cell repertoire linked to a particular immunogenetic KIR and HLA profile and CMV status. On the functional side, acute lymphoblastic leukemia (ALL) was better recognized by NK cells than acute myeloid leukemia (AML). However, a broad inter-individual disparity of NK cell responses exists against the same leukemic target, highlighting bad and good NK responders. The most effective NK cell subsets against different ALLs expressed NKG2A and represented the most frequent subset in the NK cell repertoire. In contrast, minority CD57 or/and KIR NK cell subsets were more efficient against AML. Overall, our data may help to optimize the selection of hematopoietic stem cell donors on the basis of immunogenetic KIR/HLA for ALL patients and identify the best NK cell candidates in immunotherapy for AML.

摘要

自然杀伤（NK）细胞是对抗恶性细胞的关键细胞毒性效应器。多基因和多态性的杀伤细胞免疫球蛋白样受体（KIR）及人类白细胞抗原（HLA）基因参与了NK细胞库的结构和功能形成。在本研究中，我们综合考虑这些遗传参数和巨细胞病毒（CMV）状态，广泛研究了NK细胞亚群的抗白血病潜力。基于68名献血者的NKG2A、KIR、CD57和NKG2C标志物对NK细胞亚群进行层次聚类分析，确定了供体簇，其特征为具有与特定免疫遗传KIR和HLA谱以及CMV状态相关的特定表型NK细胞库。在功能方面，NK细胞对急性淋巴细胞白血病（ALL）的识别优于急性髓系白血病（AML）。然而，针对同一白血病靶标，NK细胞反应存在广泛的个体间差异，凸显出NK反应差和反应好的个体。针对不同ALL最有效的NK细胞亚群表达NKG2A，且是NK细胞库中最常见的亚群。相反，少数CD57或/和KIR NK细胞亚群对AML更有效。总体而言，我们的数据可能有助于根据免疫遗传KIR/HLA为ALL患者优化造血干细胞供体的选择，并在AML免疫治疗中识别最佳的NK细胞候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/09efaa2bf86c/cancers-12-01927-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/304c80a47eb0/cancers-12-01927-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/a17afa5e654a/cancers-12-01927-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/fad4f8d068b8/cancers-12-01927-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/127aa1059ba4/cancers-12-01927-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/1decd6b124be/cancers-12-01927-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/09efaa2bf86c/cancers-12-01927-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/304c80a47eb0/cancers-12-01927-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/a17afa5e654a/cancers-12-01927-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/fad4f8d068b8/cancers-12-01927-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/127aa1059ba4/cancers-12-01927-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/1decd6b124be/cancers-12-01927-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bff/7409189/09efaa2bf86c/cancers-12-01927-g006.jpg

相似文献

1
Genetic and Molecular Basis of Heterogeneous NK Cell Responses against Acute Leukemia.异质性自然杀伤细胞对急性白血病反应的遗传和分子基础
Cancers (Basel). 2020 Jul 16;12(7):1927. doi: 10.3390/cancers12071927.
2
Multifactorial determinants of NK cell repertoire organization: insights into age, sex, KIR genotype, HLA typing, and CMV influence.NK 细胞 repertoire 组织的多因素决定因素：年龄、性别、KIR 基因型、HLA 分型和 CMV 影响的见解。
Front Immunol. 2024 Apr 26;15:1389358. doi: 10.3389/fimmu.2024.1389358. eCollection 2024.
3
Regulation of Adaptive NK Cells and CD8 T Cells by HLA-C Correlates with Allogeneic Hematopoietic Cell Transplantation and with Cytomegalovirus Reactivation.HLA-C对适应性自然杀伤细胞和CD8 T细胞的调控与异基因造血细胞移植及巨细胞病毒再激活相关。
J Immunol. 2015 Nov 1;195(9):4524-36. doi: 10.4049/jimmunol.1401990. Epub 2015 Sep 28.
4
Reconstitution of NK cell receptor repertoire following HLA-matched hematopoietic cell transplantation.HLA匹配的造血细胞移植后NK细胞受体库的重建。
Blood. 2003 May 1;101(9):3730-40. doi: 10.1182/blood-2002-08-2568. Epub 2003 Jan 2.
5
Adaptive single-KIRNKG2C NK cells expanded from select superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia.从精选的超级供体中扩增的适应性单 KIR-NKG2C NK 细胞表现出强大的缺失自我反应性，并能有效控制 HLA 错配的急性髓系白血病。
J Immunother Cancer. 2022 Nov;10(11). doi: 10.1136/jitc-2022-005577.
6
Co-infection of Cytomegalovirus and Epstein-Barr Virus Diminishes the Frequency of CD56NKG2AKIR NK Cells and Contributes to Suboptimal Control of EBV in Immunosuppressed Children With Post-transplant Lymphoproliferative Disorder.巨细胞病毒和 Epstein-Barr 病毒合并感染会降低 CD56<sup>NKG2A<sup>KIR<sup>NK 细胞的频率，并导致移植后淋巴组织增生性疾病免疫抑制儿童中 EBV 控制不佳。
Front Immunol. 2020 Jun 17;11:1231. doi: 10.3389/fimmu.2020.01231. eCollection 2020.
7
Donor selection for adoptive immunotherapy with NK cells in AML patients: Comparison between analysis of lytic NK cell clones and phenotypical identification of alloreactive NK cell repertoire.供体选择用于 AML 患者的过继性免疫治疗中的 NK 细胞：溶细胞 NK 细胞克隆分析与同种异体反应性 NK 细胞库的表型鉴定之间的比较。
Front Immunol. 2023 Feb 14;14:1111419. doi: 10.3389/fimmu.2023.1111419. eCollection 2023.
8
Molecular Signatures of Natural Killer Cells in CMV-Associated Anterior Uveitis, A New Type of CMV-Induced Disease in Immunocompetent Individuals.免疫功能正常个体中 CMV 相关性前葡萄膜炎的自然杀伤细胞分子特征：一种新型 CMV 诱导疾病。
Int J Mol Sci. 2021 Mar 31;22(7):3623. doi: 10.3390/ijms22073623.
9
Characterization of IFNγ-producing natural killer cells induced by cytomegalovirus reactivation after haploidentical hematopoietic stem cell transplantation.单倍体相合造血干细胞移植后巨细胞病毒再激活诱导产生γ干扰素的自然杀伤细胞的特征分析
Oncotarget. 2017 Jan 3;8(1):51-63. doi: 10.18632/oncotarget.13916.
10
The Interaction of HLA-C1/KIR2DL2/L3 Promoted KIR2DL2/L3 Single-Positive/NKG2C-Positive Natural Killer Cell Reconstitution, Raising the Incidence of aGVHD after Hematopoietic Stem Cell Transplantation.HLA-C1/KIR2DL2/L3 的相互作用促进了 KIR2DL2/L3 单阳性/NKG2C 阳性自然杀伤细胞的重建，增加了造血干细胞移植后 aGVHD 的发生率。
Front Immunol. 2022 Apr 29;13:814334. doi: 10.3389/fimmu.2022.814334. eCollection 2022.

引用本文的文献

1
Molecular Interactions Between NK Cells and Acute Leukemic Cells: KIR2DL5 Drastically Limits NK Cell Responses.自然杀伤细胞与急性白血病细胞之间的分子相互作用：KIR2DL5 极大地限制自然杀伤细胞反应。
J Clin Immunol. 2025 Jul 29;45(1):118. doi: 10.1007/s10875-025-01913-y.
2
Multifactorial determinants of NK cell repertoire organization: insights into age, sex, KIR genotype, HLA typing, and CMV influence.NK 细胞 repertoire 组织的多因素决定因素：年龄、性别、KIR 基因型、HLA 分型和 CMV 影响的见解。
Front Immunol. 2024 Apr 26;15:1389358. doi: 10.3389/fimmu.2024.1389358. eCollection 2024.
3
Contribution of the TIME in BCP-ALL: the basis for novel approaches therapeutics.

本文引用的文献

1
Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors.嵌合抗原受体修饰的自然杀伤细胞在 CD19 阳性淋巴肿瘤中的应用。
N Engl J Med. 2020 Feb 6;382(6):545-553. doi: 10.1056/NEJMoa1910607.
2
The Graft-Versus-Leukemia Effect in AML.急性髓系白血病中的移植物抗白血病效应
Front Oncol. 2019 Nov 19;9:1217. doi: 10.3389/fonc.2019.01217. eCollection 2019.
3
Intra-lineage Plasticity and Functional Reprogramming Maintain Natural Killer Cell Repertoire Diversity.谱系内可塑性和功能重编程维持自然杀伤细胞库多样性。
TIME 在 BCP-ALL 中的作用：开辟新治疗方法的基础。
Front Immunol. 2024 Jan 17;14:1325255. doi: 10.3389/fimmu.2023.1325255. eCollection 2023.
4
Analysis of the impact of handling and culture on the expansion and functionality of NK cells.分析处理和培养对 NK 细胞扩增和功能的影响。
Front Immunol. 2023 Aug 11;14:1225549. doi: 10.3389/fimmu.2023.1225549. eCollection 2023.
5
Non-Expressed Donor KIR3DL1 Alleles May Represent a Risk Factor for Relapse after T-Replete Haploidentical Hematopoietic Stem Cell Transplantation.非表达性供体KIR3DL1等位基因可能是T细胞充足的单倍体相合造血干细胞移植后复发的一个危险因素。
Cancers (Basel). 2023 May 13;15(10):2754. doi: 10.3390/cancers15102754.
6
NK cells with decreased expression of multiple activating receptors is a dominant phenotype in pediatric patients with acute lymphoblastic leukemia.多种激活受体表达降低的自然杀伤细胞是急性淋巴细胞白血病儿科患者的主要表型。
Front Oncol. 2022 Nov 7;12:1023510. doi: 10.3389/fonc.2022.1023510. eCollection 2022.
7
Natural killer cell-related prognosis signature characterizes immune landscape and predicts prognosis of HNSCC.自然杀伤细胞相关预后标志物特征描述免疫景观，并预测头颈部鳞状细胞癌的预后。
Front Immunol. 2022 Oct 3;13:1018685. doi: 10.3389/fimmu.2022.1018685. eCollection 2022.
8
Mechanisms of Immunosuppressive Tumor Evasion: Focus on Acute Lymphoblastic Leukemia.免疫抑制性肿瘤逃逸的机制：以急性淋巴细胞白血病为例。
Front Immunol. 2021 Nov 18;12:737340. doi: 10.3389/fimmu.2021.737340. eCollection 2021.
9
Making a Killer: Selecting the Optimal Natural Killer Cells for Improved Immunotherapies.制造杀手：选择最佳的自然杀伤细胞以改善免疫疗法。
Front Immunol. 2021 Oct 27;12:765705. doi: 10.3389/fimmu.2021.765705. eCollection 2021.
10
Relevance of Polymorphic KIR and HLA Class I Genes in NK-Cell-Based Immunotherapies for Adult Leukemic Patients.多态性杀伤细胞免疫球蛋白样受体（KIR）和人类白细胞抗原I类（HLA-I）基因在成人白血病患者基于自然杀伤细胞（NK细胞）的免疫治疗中的相关性
Cancers (Basel). 2021 Jul 27;13(15):3767. doi: 10.3390/cancers13153767.
Cell Rep. 2019 Nov 19;29(8):2284-2294.e4. doi: 10.1016/j.celrep.2019.10.058.
4
Human NK Cell Development: One Road or Many?人类自然杀伤细胞的发育：一条路还是多条路？
Front Immunol. 2019 Aug 29;10:2078. doi: 10.3389/fimmu.2019.02078. eCollection 2019.
5
KIR Polymorphism Modulates the Size of the Adaptive NK Cell Pool in Human Cytomegalovirus-Infected Individuals.KIR 多态性调节人类巨细胞病毒感染个体适应性 NK 细胞库的大小。
J Immunol. 2019 Oct 15;203(8):2301-2309. doi: 10.4049/jimmunol.1900423. Epub 2019 Sep 13.
6
Killers 2.0: NK cell therapies at the forefront of cancer control.杀手 2.0：NK 细胞疗法引领癌症控制新前沿。
J Clin Invest. 2019 Sep 3;129(9):3499-3510. doi: 10.1172/JCI129338.
7
A subset of HLA-DP molecules serve as ligands for the natural cytotoxicity receptor NKp44.HLA-DP 分子的一个亚类可作为自然细胞毒性受体 NKp44 的配体。
Nat Immunol. 2019 Sep;20(9):1129-1137. doi: 10.1038/s41590-019-0448-4. Epub 2019 Jul 29.
8
Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion.NKG2D 配体的缺失定义了白血病干细胞，并介导其免疫逃逸。
Nature. 2019 Aug;572(7768):254-259. doi: 10.1038/s41586-019-1410-1. Epub 2019 Jul 17.
9
Chronic stimulation drives human NK cell dysfunction and epigenetic reprograming.慢性刺激导致人类自然杀伤细胞功能障碍和表观遗传重编程。
J Clin Invest. 2019 Jun 18;129(9):3770-3785. doi: 10.1172/JCI125916.
10
Impact of KIR/HLA Incompatibilities on NK Cell Reconstitution and Clinical Outcome after T Cell-Replete Haploidentical Hematopoietic Stem Cell Transplantation with Posttransplant Cyclophosphamide.KIR/HLA 不相容对 T 细胞耗竭的单倍体造血干细胞移植后环磷酰胺治疗后 NK 细胞重建和临床结果的影响。
J Immunol. 2019 Apr 1;202(7):2141-2152. doi: 10.4049/jimmunol.1801489. Epub 2019 Feb 20.