造血干细胞移植中KIR及其配体影响移植预后的研究进展

徐郑丽; 赵翔宇

doi:10.13201/j.issn.1004-2806.2021.01.016

造血干细胞移植中KIR及其配体影响移植预后的研究进展

徐郑丽,
赵翔宇^,

- 北京大学人民医院北京大学血液病研究所国家血液系统疾病临床医学研究中心造血干细胞移植北京市重点实验室(北京, 100044)
基金项目:
国家自然科学基金面上项目(No:81670166)

国家自然科学基金创新研究群体项目(No:81621001)

北京市科技计划课题(No:Z171100001017098)

详细信息

通讯作者: 赵翔宇,E-mail:zhao_xy@bjmu.edu.cn

中图分类号: R551.3

收稿日期: 2020-06-08

Progress on the effect of KIR and its ligands on the prognosis of hematopoietic stem cell transplantation

XU Zhengli,
ZHAO Xiangyu^,

More Information

Corresponding author: ZHAO Xiangyu, E-mail: zhao_xy@bjmu.edu.cn

Received Date: 08 June 2020

摘要

摘要: 造血干细胞移植是绝大多数血液系统疾病的有效治愈方法。移植失败的主要原因包括移植物抗宿主病（graft versus host disease,GVHD）、严重感染以及疾病复发,而上述主要合并症的预后与移植后免疫重建密切相关^[1-2]。移植后免疫重建包括固有免疫重建及适应性免疫重建。其中,固有免疫重建尤其是自然杀伤细胞（NK细胞）的重建时间早于适应性免疫,这有利于移植后早期对肿瘤和病原体的防御,与移植后移植物抗宿主病、感染及复发密切相关^[3]。NK细胞有效发挥抗肿瘤及抗感染作用依赖于成熟功能的获得;既往研究认为NK细胞功能的获得主要依赖于NK细胞教育,是NK细胞表面杀伤免疫球蛋白受体（killer cell immunoglobulin like receptor,KIR）与自身人类白细胞抗原（HLA）相互识别的过程（表1）。
- 造血干细胞移植 /
- 杀伤性免疫球蛋白受体 /
- 配体
Abstract: Natural killer cells(NK cells) are important components of innate immunity. Killer cell immunoglobulin like receptor(KIR) of NK cells influences the prognosis of relapse, infection and graft versus host disease after transplantation through NK cell alloreactivity. Under different transplantation modes, HLA-KIR interaction has indicated different effects on transplantation prognosis, and the current research results have not been unified. In this review, the effects of HLA-KIR interaction on transplantation prognosis from different donors have been respectively reviewed.
- hematopoietic stem cell transplantation /
- killer immunoglobulin receptor /
- ligand

HTML全文

参考文献(40)

[1]	刘微,王倩,王茫桔,等.异基因造血干细胞移植后巨细胞病毒再活化对急性髓系白血病复发和生存的影响[J].临床血液学杂志,2019,32(3):177-181.
[2]	冯一梅,张曦.重视慢性移植物抗宿主病的临床管理[J].临床血液学杂志,2019,32(9):651-655.
[3]	Ullah MA,Hill GR,Tey SK.Functional Reconstitution of Natural Killer Cells in Allogeneic Hematopoietic Stem Cell Transplantation[J].Front Immunol,2016,7:144.
[4]	Cooley S,Parham P,Miller JS.Strategies to activate NK cells to prevent relapse and induce remission following hematopoietic stem cell transplantation[J].Blood,2018,131(10):1053-1062.
[5]	Beksaç M,Dalva K.Role of killer immunoglobulin-like receptor and ligand matching in donor selection[J].Bone Marrow Res,2012,2012:271695.
[6]	Björklund AT,Schaffer M,Fauriat C,et al.NK cells expressing inhibitory KIR for non-self-ligands remain tolerant in HLA-matched sibling stem cell transplantation[J].Blood,2010,115(13):2686-2694.
[7]	Yu J,Venstrom JM,Liu XR,et al.Breaking tolerance to self,circulating natural killer cells expressing inhibitory KIR for non-self HLA exhibit effector function after T cell-depleted allogeneic hematopoietic cell transplantation[J].Blood,2009,113(16):3875-3884.
[8]	Hsu KC,Keever-Taylor CA,Wilton A,et al.Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes[J].Blood,2005,105(12):4878-4884.
[9]	Shimoni A,Vago L,Bernardi M,et al.Missing HLA C group 1 ligand in patients with AML and MDS is associated with reduced risk of relapse and better survival after allogeneic stem cell transplantation with fludarabine and treosulfan reduced toxicity conditioning[J].Am J Hematol,2017,92(10):1011-1019.
[10]	Khanuntong S,Kuptawintu P,Upaisilpsathaporn K,et al.The effect of missing KIR ligands,activating KIR genotype and haplotype on the outcome of T-cell-replete hematopoietic stem cell transplantation from HLA-identical siblings in Thai patients[J].HLA,2016,87(6):422-431.
[11]	Clausen J,Kircher B,Auberger J,et al.The role of missing killer cell immunoglobulin-like receptor ligands in T cell replete peripheral blood stem cell transplantation from HLA-identical siblings[J].Biol Blood Marrow Transplant,2010,16(2):273-280.
[12]	Miller JS,Cooley S,Parham P,et al.Missing KIR ligands are associated with less relapse and increased graft-versus-host disease(GVHD)following unrelated donor allogeneic HCT[J].Blood,2007,109(11):5058-5061.
[13]	Hsu KC,Gooley T,Malkki M,et al.International Histocompatibility Working,KIR ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy[J].Biol Blood Marrow Transplant,2006,12(8):828-836.
[14]	Giebel S,Locatelli F,Lamparelli T,et al.Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors[J].Blood,2003,102(3):814-819.
[15]	Gagne K,Busson M,Bignon JD,et al.Donor KIR3DL1/3DS1 gene and recipient Bw4 KIR ligand as prognostic markers for outcome in unrelated hematopoietic stem cell transplantation[J].Biol Blood Marrow Transplant,2009,15(11):1366-1375.
[16]	Boudreau JE,Giglio F,Gooley TA,et al.KIR3DL1/HLA-B Subtypes Govern Acute Myelogenous Leukemia Relapse After Hematopoietic Cell Transplantation[J].J Clin Oncol,2017,35(20):2268-2278.
[17]	Sahin U,Dalva K,Gungor F,et al.Donor-recipient killer immunoglobulin like receptor(KIR)genotype matching has a protective effect on chronic graft versus host disease and relapse incidence following HLA-identical sibling hematopoietic stem cell transplantation[J].Ann Hematol,2018,97(6):1027-1039.
[18]	Elfishawi SM,Mossallam GI,El-Fattah RA,et al.The effect of killer cell immunoglobulin-like receptor genotype on outcome of hematopoietic stem cell transplantation from matched sibling[J].Hum Immunol,2017,78(11/12):684-691.
[19]	Cardozo DM,Marangon AV,da Silva RF,et al.Synergistic effect of KIR ligands missing and cytomegalovirus reactivation in improving outcomes of haematopoietic stem cell transplantation from HLA-matched sibling donor for treatment of myeloid malignancies[J].Hum Immunol,2016,77(10):861-868.
[20]	Yabe T,Matsuo K,Hirayasu K,et al.Donor killer immunoglobulin-like receptor(KIR)genotype-patient cognate KIR ligand combination and antithymocyte globulin preadministration are critical factors in outcome of HLA-C-KIR ligand-mismatched T cell-replete unrelated bone marrow transplantation[J].Biol Blood Marrow Transplant,2008,14(1):75-87.
[21]	Bao XJ,Hou LH,Sun AN,et al.The impact of KIR2DS4 alleles and the expression of KIR in the development of acute GVHD after unrelated allogeneic hematopoietic SCT[J].Bone Marrow Transplant,2010,45(9):1435-1441.
[22]	Gaafar A,Sheereen A,Almohareb F,et al.Prognostic role of KIR genes and HLA-C after hematopoietic stem cell transplantation in a patient cohort with acute myeloid leukemia from a consanguineous community[J].Bone Marrow Transplant,2018,53(9):1170-1179.
[23]	Cook M,Briggs D,Craddock C,et al.Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following T-cell replete stem cell transplantation[J].Blood,2006,107(3):1230-1232.
[24]	Schaffer M,Malmberg KJ,Ringdén O,et al.Increased infection-related mortality in KIR-ligand-mismatched unrelated allogeneic hematopoietic stem-cell transplantation[J].Transplantation,2004,78(7):1081-1085.
[25]	Ruggeri L,Capanni M,Urbani E,et al.Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants[J].Science,2002,295(5562):2097-2100.
[26]	Ruggeri L,Mancusi A,Capanni M,et al.Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia:challenging its predictive value[J].Blood,2007,110(1):433-440.
[27]	Chen DF,Prasad VK,Broadwater G,et al.Differential impact of inhibitory and activating Killer Ig-Like Receptors(KIR)on high-risk patients with myeloid and lymphoid malignancies undergoing reduced intensity transplantation from haploidentical related donors[J].Bone Marrow Transplant,2012,47(6):817-823.
[28]	Willem C,Makanga DR,Guillaume T,et al.Impact of KIR/HLA Incompatibilities on NK Cell Reconstitution and Clinical Outcome after T Cell-Replete Haploidentical Hematopoietic Stem Cell Transplantation with Posttransplant Cyclophosphamide[J].J Immunol,2019,202(7):2141-2152.
[29]	Shimoni A,Labopin M,Lorentino F,et al.Killer cell immunoglobulin-like receptor ligand mismatching and outcome after haploidentical transplantation with post-transplant cyclophosphamide[J].Leukemia,2019,33(1):230-239.
[30]	Huang XJ,Zhao XY,Liu DH,et al.Deleterious effects of KIR ligand incompatibility on clinical outcomes in haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion[J].Leukemia,2007,21(4):848-851.
[31]	Zhao XY,Huang XJ,Liu KY,et al.Prognosis after unmanipulated HLA-haploidentical blood and marrow transplantation is correlated to the numbers of KIR ligands in recipients[J].Eur J Haematol,2007,78(4):338-346.
[32]	Zhao XY,Chang YJ,Xu LP,et al.HLA and KIR genotyping correlates with relapse after T-cell-replete haploidentical transplantation in chronic myeloid leukaemia patients[J].Br J Cancer,2014,111(6):1080-1088.
[33]	Michaelis SU,Mezger M,Bornhäuser M,et al.KIR haplotype B donors but not KIR-ligand mismatch result in a reduced incidence of relapse after haploidentical transplantation using reduced intensity conditioning and CD3/CD19-depleted grafts[J].Ann Hematol,2014,93(9):1579-1586.
[34]	Oevermann L,Michaelis SU,Mezger M,et al.KIR B haplotype donors confer a reduced risk for relapse after haploidentical transplantation in children with ALL[J].Blood,2014,124(17):2744-2747.
[35]	Symons HJ,Leffell MS,Rossiter ND,et al.Improved survival with inhibitory killer immunoglobulin receptor(KIR)gene mismatches and KIR haplotype B donors after nonmyeloablative,HLA-haploidentical bone marrow transplantation[J].Biol Blood Marrow Transplant,2010,16(4):533-542.
[36]	Bastos-Oreiro M,Anguita J,Martínez-Laperche C,et al.Inhibitory killer cell immunoglobulin-like receptor(iKIR)mismatches improve survival after T-cell-repleted haploidentical transplantation[J].Eur J Haematol,2016,96(5):483-491.
[37]	Bishara A,De Santis D,Witt CC,et al.The beneficial role of inhibitory KIR genes of HLA class I NK epitopes in haploidentically mismatched stem cell allografts may be masked by residual donor-alloreactive T cells causing GVHD[J].Tissue Antigens,2004,63(3):204-211.
[38]	Torío A,Pascual MJ,Vidales I,et al.Donor Selection Based on Killer Cell Immunoglobulin-Like Receptor(KIR)Genotype May Improve Outcome After T-Cell-Replete Haploidentical Transplantation[J].Transplant Proc,2018,50(2):679-682.
[39]	Mancusi A,Ruggeri L,Urbani E,et al.Haploidentical hematopoietic transplantation from KIR ligand-mismatched donors with activating KIRs reduces nonrelapse mortality[J].Blood,2015,125(20):3173-3182.
[40]	Zhao XY,Luo XY,Yu XX,et al.Recipient-donor KIR ligand matching prevents CMV reactivation post-haploidentical T cell-replete transplantation[J].Br J Haematol,2017,177(5):766-781.