Введение

bloodjour

Гематология и трансфузиология

Russian journal of hematology and transfusiology

0234-57302411-3042

ООО Издательский дом «Практика»

10.35754/0234-5730-2022-67-4-551-569

bloodjour-410

Research Article

ОБЗОРЫ

REVIEWS

Влияние генов киллерных иммуноглобулинподобных рецепторов натуральных киллерных клеток и их HLA-лигандов на результаты трансплантации аллогенных гемопоэтических стволовых клеток

Impact of natural killer cell’s functional reconstruction on the results of allogeneic hematopoietic stem cell transplantation

https://orcid.org/0000-0002-5569-0155

Конова

З. В.

Konova

Z. V.

Конова Зоя Викторовна, кандидат медицинских наук, гематолог отделения интенсивной высокодозной химиотерапии и трансплантации костного мозга

125167, Москва

Zoya V. Konova, Cand. Sci. (Med.), Hematologist of the Department of Highdose Chemotherapy and BMT

125167, Moscow

konova.zoya@gmail.com

https://orcid.org/0000-0001-6177-3566

Паровичникова

Е. Н.

Parovichnikova

E. N.

Паровичникова Елена Николаевна, доктор медицинских наук, генеральный директор

125167, Москва

Elena N. Parovichnikova, Dr. Sci. (Med.), CEO

125167, Moscow

parovichnikova.e@blood.ru

https://orcid.org/0000-0002-8490-6066

Гальцева

И. В.

Galtseva

I. V.

Гальцева Ирина Владимировна, кандидат медицинских наук, заведующая научно-клинической лабораторией иммунофенотипирования клетоккрови и костного мозга

125167, Москва

Irina V. Galtseva, Cand. Sci. (Med.), Head of the Scientific and Clinical Laboratory for Immunophenotyping of Blood and Bone Marrow Cells

125167, Moscow

irinagaltseva@gmail.com

https://orcid.org/0000-0002-0110-3314

Хамаганова

Е. Г.

Khamaganova

E. G.

Хамаганова Екатерина Георгиевна, доктор биологических наук, заведующая лабораторией тканевого типирования

125167, Москва

Ekaterina G. Khamaganova, Dr. Sci. (Biol.), Head of the Tissue Typing Laboratory

125167, Moscow

ekhamag@mail.ru

ФГБУ «Национальный медицинский исследовательский центр гематологии» Министерства здравоохранения Российской ФедерацииРоссияNational Medical Research Center for HematologyRussian Federation

2022

27122022

674551569

2022

Конова З.В., Паровичникова Е.Н., Гальцева И.В., Хамаганова Е.Г.

Konova Z.V., Parovichnikova E.N., Galtseva I.V., Khamaganova E.G.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.htjournal.ru/jour/article/view/410

Введение

Введение. Ключевым направлением развития технологий трансплантации аллогенных гемопоэтических стволовых клеток (алло-ТГСК) является разработка стратегий, предотвращающих развитие реакции «трансплантат против хозяина» (РТПХ) и уменьшающих риск возникновения инфекционных осложнений при сохранении противоопухолевого эффекта – реакции «трансплантат против лейкоза» (РТПЛ).

Цель – анализ биологических и функциональных свойств натуральных киллеров (НК-клеток) после алло-ТГСК, их реконституции после алло-ТГСК и факторов, влияющих на этот процесс, а также механизмов аллореактивности НК-клеток у больных после алло-ТГСК.

Основные сведения

Основные сведения. Функции НК-клеток регулируются различными типами рецепторов, активирующих или ингибирующих НК-зависимый цитолиз, которые экспрессируются на НК-клетках. Среди них основную роль играют киллерные иммуноглобулин-подобные рецепторы (KIR), которые опосредуют развитие толерантности к собственным клеткам и иммунный ответ, как противоопухолевый, так и направленный против инфекционных агентов. НК-клетки могут играть решающую роль в предотвращении ранних рецидивов и инфекционных осложнений, так как восстанавливаются одними из первых после алло-ТГСК. Они также обладают способностью устранять Т-клетки и антиген-презентирующие клетки реципиента, тем самым предотвращая развитие несостоятельности трансплантата и РТПХ. Существует несколько моделей НК-аллореактивности с участием KIR, однако результаты исследований в этой области противоречивы.

Introduction. Currently, more and more attention is being paid to possible strategies for preventing the development of graft-versus-host disease (GVHD) and reducing the risk of infections while maintaining the antitumor effect — graft-versus-leukemia effect (GVL). In this context, the study of natural killer cells (NK-cells) seems to be quite promising.

Aim – to analyze the biological and functional properties of NK-cells after allo-HSCT, their reconstitution after transplantation and factors affecting this process, as well as the mechanisms of alloreactivity of NK cells in patients after allo-HSCT. Main findings. Various types of activating or inhibiting receptors, which are expressed on NK-cells, regulate the functions of NK-cells. Among them, the main role is played by the killer immunoglobin-like receptor (KIR-receptor), which mediates tolerance to one’s own cells and the immune response, both antitumor and directed against infectious agents. NK-cells can play a decisive role in preventing early relapses and infectious complications, as they are among the first to recover after allo-HSCT. They also have the ability to eliminate the recipient’s T-cells and antigen presenting cells (APCs), thereby preventing the development of graft failure and GVHD. There are several models of NK alloreactivity based on KIR; however, the results of studies in this area are contradictory. This review summarizes the available literature data.

натуральные киллерыкиллерный иммуноглобулин-подобный рецептортрансплантация аллогенных гемопоэтических стволовых клеток

natural killer cellskiller immunoglobin-like receptorallogeneic hematopoietic stem cells transplantation

References1

Савченко В.Г., Менделеева Л.П., Клясова Г.А. и др. Эффективность трансплантации аллогенного костного мозга у больных острыми лейкозами в фазе полной ремиссии и у больных хроническим миелолейкозом в хронической фазе. Терапевтический архив. 1999; 71(7): 27–32.

Savchenko V.G., Mendeleeva L.P., Klyasova G.A., et al. Efficiency of allogeneous bone marrow transplantation in patients with acute leukemia in the phase of complete remission and in patients with chronic myelukemia in the chronic phase. Therapevticheskii arkhiv. 1999; 71(7): 27–32. (In Russian).

Holmqvist A.S., Chen Y., Wu J., et al. Assessment of late mortality risk after allogeneic blood or marrow transplantation performed in childhood. JAMA Oncol. 2018; 4(12): e182453. DOI: 10.1001/jamaoncol.2018.2453.

Styczyński J., Tridello G., Koster L., et al. Death after hematopoietic stem cell transplantation: Changes over calendar year time, infections and associated factors. Bone Marrow Transplant. 2020; 55(1): 126–36. DOI: 10.1038/s41409-019-0624-z.

Vivier E., Tomasello E., Baratin M., et al. Functions of natural killer cells. Nat Immunol. 2008; 9(5): 503–10. DOI: 10.1038/ni1582.

Pegram H.J., Andrews D.M., Smyth M.J., et al. Activating and inhibitory receptors of natural killer cells. Immunol Cell Biol. 2011; 89(2): 216–24. DOI: 10.1038/icb.2010.78.

Wilson M.J., Torkar M., Trowsdale J. Genomic organization of a human killer cell inhibitory receptor gene. Tissue Antigens. 1997; 49(6): 574–9. DOI: 10.1111/j.1399-0039.1997.tb02804.x.

Hsu K.C., Chida S., Geraghty D.E., Dupont B. The killer cell immunoglobulin-like receptor (KIR) genomic region: Gene-order, haplotypes and allelic polymorphism. Immunol Rev. 2002; 190: 40–52. DOI: 10.1034/j.1600-065X.2002.19004.x.

Manser A.R., Weinhold S., Uhrberg M. Human KIR repertoires: Shaped by genetic diversity and evolution. Immunol Rev. 2015; 267(1): 178–96. DOI: 10.1111/imr.12316.

Cooley S., Weisdorf D.J., Guethlein L.A., et al. Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood. 2010; 116(14): 2411–9. DOI: 10.1182/blood-2010-05-283051.

Leung W. Use of NK cell activity in cure by transplant. Br J Haematol. 2011; 155(1): 14–29. DOI: 10.1111/j.1365-2141.2011.08823.x.

Björklund A.T., Schaffer M., Fauriat C., et al. NK cells expressing inhibitory KIR for non-self-ligands remain tolerant in HLA-matched sibling stem cell transplantation. Blood. 2010; 115(13): 2686–94. DOI: 10.1182/blood-2009-07-229740.

Pende D., Marcenaro S., Falco M., et al. Anti-leukemia activity of alloreactive NK cells in KIR ligand-mismatched haploidentical HSCT for pediatric patients: Evaluation of the functional role of activating KIR and redefinition of inhibitory KIR specificity. Blood. 2009; 113(13): 3119–29. DOI: 10.1182/blood-2008-06-164103.

Ogonek J., Kralj Juric M., Ghimire S., et al. Immune reconstitution after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016; 7: 507. DOI: 10.3389/fimmu.2016.00507.

Hu B., Bao G., Zhang Y., et al. Donor NK cells and IL-15 promoted engraftment in nonmyeloablative allogeneic bone marrow transplantation. J Immunol. 2012; 189(4): 1661–70. DOI: 10.4049/jimmunol.1103199.

Moretta L., Montaldo E., Vacca P., et al. Human natural killer cells: Origin, receptors, function, and clinical applications. Int Arch Allergy Immunol. 2014; 164(4): 253–64. DOI: 10.1159/000365632.

Hattori N., Nakamaki T. Natural killer immunotherapy for minimal residual disease eradication following allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia. Int J Mol Sci. 2019; 20(9): 2057. DOI: 10.3390/ijms20092057.

Ruggeri L., Capanni M., Urbani E., et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002; 295(5562): 2097–100. DOI: 10.1126/science.1068440.

Leung W., Iyengar R., Turner V., et al. Determinants of antileukemia effects of allogeneic NK cells. J Immunol. 2004; 172(1): 644–50. DOI: 10.4049/jimmunol.172.1.644.

Cooley S., Trachtenberg E., Bergemann T.L., et al. Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia. Blood. 2009; 113(3): 726–32. DOI: 10.1182/blood-2008-07-171926.

Chewning J.H., Gudme C.N., Hsu K.C., et al. KIR2DS1-positive NK cells mediate alloresponse against the C2 HLA-KIR ligand group in vitro. J Immunol. 2007; 179(2): 854–68. DOI: 10.4049/jimmunol.179.2.854.

Montaldo E., Del Zotto G., Della Chiesa M., et al. Human NK cell receptors/markers: A tool to analyze NK cell development, subsets and function. Cytometry A. 2013; 83(8): 702–13. DOI: 10.1002/cyto.a.22302.

Caligiuri M.A. Human natural killer cells. Blood. 2008; 112(3): 461–9. DOI: 10.1182/blood-2007-09-077438.

Locatelli F., Pende D., Falco M., et al. NK cells mediate a crucial graft-versus-leukemia effect in haploidentical-HSCT to cure high-risk acute leukemia. Trends Immunol. 2018; 39(7): 577–90. DOI: 10.1016/J.IT.2018.04.009.

Vago L., Forno B., Sormani M.P., et al. Temporal, quantitative, and functional characteristics of single-KIR-positive alloreactive natural killer cell recovery account for impaired graft-versus-leukemia activity after haploidentical hematopoietic stem cell transplantation. Blood. 2008; 112(8): 3488–99. DOI: 10.1182/blood-2007-07-103325.

Abel A.M., Yang C., Thakar M.S., et al. Natural killer cells: Development, maturation, and clinical utilization. Front Immunol. 2018; 9: 1869. DOI: 10.3389/fimmu.2018.01869.

Foley B., Cooley S., Verneris M.R., et al. NK cell education after allogeneic transplantation: Dissociation between recovery of cytokine-producing and cytotoxic functions. Blood. 2011; 118(10): 2784–92. DOI: 10.1182/blood-2011-04-347070.

Schönberg K., Fischer J.C., Kögler G., Uhrberg M. Neonatal NK-cell repertoires are functionally, but not structurally, biased toward recognition of self HLA class I. Blood. 2011; 117(19): 5152–6. DOI: 10.1182/blood-2011-02-334441.

Rathmann S., Glatzel S., Schönberg K., et al. Expansion of NKG2A-LIR1- natural killer cells in HLA-matched, killer cell immunoglobulin-like receptors/HLA-ligand mismatched patients following hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2010; 16(4): 469–81. DOI: 10.1016/j.bbmt.2009.12.008.

Moretta L., Locatelli F., Pende D., et al. Killer Ig-like receptor-mediated control of natural killer cell alloreactivity in haploidentical hematopoietic stem cell transplantation. Blood. 2011; 117(3): 764–71. DOI: 10.1182/blood-2010-08-264085.

Elliott J.M., Yokoyama W.M. Unifying concepts of MHC-dependent natural killer cell education. Trends Immunol. 2011; 32(8): 364–72. DOI: 10.1016/J.IT.2011.06.001.

Zhao X.-Y., Yu X.-X., Xu Z.-L., et al. Donor and host coexpressing KIR ligands promote NK education after allogeneic hematopoietic stem cell transplantation. Blood Adv. 2019; 3(24): 4312–25. DOI: 10.1182/bloodadvances.2019000242.

Kao R.L., Holtan S.G. Host and graft factors impacting infection risk in hematopoietic cell transplantation. Infect Dis Clin North Am. 2019; 33(2): 311–29. DOI: 10.1016/j.idc.2019.02.001.

Schaffer M., Malmberg K.-J., Ringdén O., et al. Increased infection-related mortality in KIR-ligand-mismatched unrelated allogeneic hematopoietic stem-cell transplantation. Transplantation. 2004; 78(7): 1081–5. DOI: 10.1097/01.tp.0000137103.19717.86.

Zhao X.-Y., Luo X.-Y., Yu X.-X., et al. Recipient-donor KIR ligand matching prevents CMV reactivation post-haploidentical T cell-replete transplantation. Br J Haematol. 2017; 177(5): 766–81. DOI: 10.1111/bjh.14622.

Zaia J.A., Sun J.Y., Gallez-Hawkins G.M., et al. The effect of single and combined activating killer immunoglobulin-like receptor genotypes on cytomegalovirus infection and immunity after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2009; 15(3): 315–25. DOI: 10.1016/j.bbmt.2008.11.030.

Tomblyn M., Young J.-A.H., Haagenson M.D., et al. Decreased infections in recipients of unrelated donor hematopoietic cell transplantation from donors with an activating KIR genotype. Biol Blood Marrow Transplant. 2010; 16(8): 1155–61. DOI: 10.1016/j.bbmt.2010.02.024.

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. Blood. 2006; 107(3): 1230–2. DOI: 10.1182/blood-2005-03-1039.

Wu X., He J., Wu D., et al. KIR and HLA-Cw genotypes of donor-recipient pairs influence the rate of CMV reactivation following non-T-cell deleted unrelated donor hematopoietic cell transplantation. Am J Hematol. 2009; 84(11): 776–7. DOI: 10.1002/ajh.21527.

Gallez-Hawkins G.M., Franck A.E., Li X., et al. Expression of activating KIR2DS2 and KIR2DS4 genes after hematopoietic cell transplantation: Relevance to cytomegalovirus infection. Biol Blood Marrow Transplant. 2011; 17(11): 1662–72. DOI: 10.1016/j.bbmt.2011.04.008.

Mancusi A., Ruggeri L., Urbani E., et al. Haploidentical hematopoietic transplantation from KIR ligand-mismatched donors with activating KIRs reduces nonrelapse mortality. Blood. 2015; 125(20): 3173–82. DOI: 10.1182/blood-2014-09-599993.

Chen C., Busson M., Rocha V., et al. Activating KIR genes are associated with CMV reactivation and survival after non-T-cell depleted HLA-identical sibling bone marrow transplantation for malignant disorders. Bone Marrow Transplant. 2006; 38(6): 437–44. DOI: 10.1038/sj.bmt.1705468.

Bultitude W.P., Schellekens J., Szydlo R.M., et al. Presence of donor-encoded centromeric KIR B content increases the risk of infectious mortality in recipients of myeloablative, T-cell deplete, HLA-matched HCT to treat AML. Bone Marrow Transplant. 2020; 55(10): 1975–84. DOI: 10.1038/s41409-020-0858-9.

Cooley S., McCullar V., Wangen R., et al. KIR reconstitution is altered by T cells in the graft and correlates with clinical outcomes after unrelated donor transplantation. Blood. 2005; 106(13): 4370–6. DOI: 10.1182/blood-2005-04-1644.

Della Chiesa M., Falco M., Podestà M., et al. Phenotypic and functional heterogeneity of human NK cells developing after umbilical cord blood transplantation: A role for human cytomegalovirus? Blood. 2012; 119(2): 399–410. DOI: 10.1182/blood-2011-08-372003.

Jin F., Lin H., Gao S., et al. Characterization of IFNγ-producing natural killer cells induced by cytomegalovirus reactivation after haploidentical hematopoietic stem cell transplantation. Oncotarget. 2017; 8(1): 51–63. DOI: 10.18632/oncotarget.13916.

Foley B., Cooley S., Verneris M.R., et al. Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function. Blood. 2012; 119(11): 2665–74. DOI: 10.1182/blood-2011-10-386995.

Davis Z.B., Cooley S.A., Cichocki F., et al. Adaptive natural killer cell and killer cell immunoglobulin-like receptor-expressing T cell responses are induced by cytomegalovirus and are associated with protection against cytomegalovirus reactivation after allogeneic donor hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015; 21(9): 1653–62. DOI: 10.1016/j.bbmt.2015.05.025.

Yu H., Tian Y., Wang Y., et al. Dendritic cell regulation of graft-vs.-host disease: Immunostimulation and tolerance. Front Immunol. 2019; 10: 93. DOI: 10.3389/fimmu.2019.00093.

Champlin R.E., Passweg J.R., Zhang M.J., et al. T-cell depletion of bone marrow transplants for leukemia from donors other than HLA-identical siblings: Advantage of T-cell antibodies with narrow specificities. Blood. 2000; 95(12): 3996–4003.

Murphy W.J., Bennett M., Kumar V., Longo D.L. Donor-type activated natural killer cells promote marrow engraftment and B cell development during allogeneic bone marrow transplantation. J Immunol. 1992; 148(9): 2953–60.

Asai O., Longo D.L., Tian Z.G., et al. Suppression of graft-versus-host disease and amplification of graft-versus-tumor effects by activated natural killer cells after allogeneic bone marrow transplantation. J Clin Invest. 1998; 101(9): 1835–42. DOI: 10.1172/JCI1268.

Olson J.A., Leveson-Gower D.B., Gill S., et al. NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects. Blood. 2010; 115(21): 4293–301. DOI: 10.1182/blood-2009-05-222190.

Hüber C.M., Doisne J.-M., Colucci F. IL-12/15/18-preactivated NK cells suppress GvHD in a mouse model of mismatched hematopoietic cell transplantation. Eur J Immunol. 2015; 45(6): 1727–35. DOI: 10.1002/eji.201445200.

Jaiswal S.R., Zaman S., Nedunchezhian M., et al. CD56-enriched donor cell infusion after post-transplantation cyclophosphamide for haploidentical transplantation of advanced myeloid malignancies is associated with prompt reconstitution of mature natural killer cells and regulatory T cells with reduced incidence of acute graft versus host disease: A pilot study. Cytotherapy. 2017; 19(4): 531–42. DOI: 10.1016/j.jcyt.2016.12.006.

Shah N.N., Baird K., Delbrook C.P., et al. Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell-depleted stem cell transplantation. Blood. 2015; 125(5): 784–92. DOI: 10.1182/blood-2014-07-592881.

Verneris M.R., Miller J.S., Hsu K.C., et al. Investigation of donor KIR content and matching in children undergoing hematopoietic cell transplantation for acute leukemia. Blood Adv. 2020; 4(7): 1350–6. DOI: 10.1182/bloodadvances.2019001284.

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. Blood. 2007; 110(1): 433–40. DOI: 10.1182/blood-2006-07-038687.

Cardozo D.M., Marangon A.V., da Silva R.F., 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. Hum Immunol. 2016; 77(10): 861–8. DOI: 10.1016/j.humimm.2016.07.003.

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. Bone Marrow Transplant. 2018; 53(9): 1170–9. DOI: 10.1038/s41409-018-0123-7.

Sobecks R.M., Wang T., Askar M., et al. Impact of KIR and HLA genotypes on outcomes after reduced-intensity conditioning hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015; 21(9): 1589–96. DOI: 10.1016/j.bbmt.2015.05.002.

Willem C., Makanga D.R., 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 Immunol. 2019; 202(7): 2141–52. DOI: 10.4049/jimmunol.1801489.

Shilling H.G., McQueen K.L., Cheng N.W., et al. Reconstitution of NK cell receptor repertoire following HLA-matched hematopoietic cell transplantation. Blood. 2003; 101(9): 3730–40. DOI: 10.1182/blood-2002-08-2568.

Fallen P.R., McGreavey L., Madrigal J.A., et al. Factors affecting reconstitution of the T cell compartment in allogeneic haematopoietic cell transplant recipients. Bone Marrow Transplant. 2003; 32(10): 1001–14. DOI: 10.1038/sj.bmt.1704235.

Ciurea S.O., Mulanovich V., Saliba R.M., et al. Improved early outcomes using a T cell replete graft compared with T cell depleted haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2012; 18(12): 1835–44. DOI: 10.1016/j.bbmt.2012.07.003.

van Bergen J., Thompson A., van der Slik A., et al. Phenotypic and functional characterization of CD4 T cells expressing killer Ig-like receptors. J Immunol. 2004; 173(11): 6719–26. DOI: 10.4049/jimmunol.173.11.6719.

Pradier A., Papaserafeim M., Li N., et al. Small-molecule immunosuppressive drugs and therapeutic immunoglobulins differentially inhibit NK cell effector functions in vitro. Front Immunol. 2019; 10: 556. DOI: 10.3389/fimmu.2019.00556.

Venstrom J.M., Gooley T.A., Spellman S., et al. Donor activating KIR3DS1 is associated with decreased acute GVHD in unrelated allogeneic hematopoietic stem cell transplantation. Blood. 2010; 115(15): 3162–5. DOI: 10.1182/blood-2009-08-236943.

Heatley S.L., Mullighan C.G., Doherty K., et al. Activating killer-cell immunoglobulin-like receptor haplotype influences clinical outcome following HLA-matched sibling haematopoietic stem cell transplantation. HLA. 2018; 92(2): 74–82. DOI: 10.1111/tan.13327.

Sivori S., Carlomagno S., Falco M., et al. Natural killer cells expressing the KIR2DS1-activating receptor efficiently kill T-cell blasts and dendritic cells: Implications in haploidentical HSCT. Blood. 2011; 117(16): 4284–92. DOI: 10.1182/blood-2010-10-316125.

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. Ann Hematol. 2018; 97(6): 1027–39. DOI: 10.1007/s00277-018-3274-0.

Bachanova V., Weisdorf D.J., Wang T., et al. Donor KIR B genotype improves progression-free survival of non-Hodgkin lymphoma patients receiving unrelated donor transplantation. Biol Blood Marrow Transplant. 2016; 22(9): 1602–7. DOI: 10.1016/j.bbmt.2016.05.016.

Burns L.J., Weisdorf D.J., DeFor T.E., et al. Enhancement of the anti-tumor activity of a peripheral blood progenitor cell graft by mobilization with interleukin 2 plus granulocyte colony-stimulating factor in patients with advanced breast cancer. Exp Hematol. 2000; 28(1): 96–103. DOI: 10.1016/s0301-472x(99)00129-0.

Introna M., Borleri G., Conti E., et al. Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: A phase I study. Haematologica. 2007; 92(7): 952–9. DOI: 10.3324/haematol.11132.

Passweg J.R., Tichelli A., Meyer-Monard S., et al. Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia. 2004; 18(11): 1835–8. DOI: 10.1038/sj.leu.2403524.

Srour S.A., Saliba R.M., Bittencourt M.C.B., et al. Haploidentical transplantation for acute myeloid leukemia patients with minimal/measurable residual disease at transplantation. Am J Hematol. 2019; 94(12): 1382–7. DOI: 10.1002/ajh.25647.

Giebel S., Locatelli F., Lamparelli T., et al. Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood. 2003; 102(3): 814–9. DOI:10.1182/blood-2003-01-0091.

Elmaagacli A.H., Ottinger H., Koldehoff M., et al. Reduced risk for molecular disease in patients with chronic myeloid leukemia after transplantation from a KIR-mismatched donor. Transplantation. 2005; 79(12): 1741–7. DOI: 10.1097/01.tp.0000164500.16052.3c.

Michaelis S.U., 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. Ann Hematol. 2014; 93(9): 1579–86. DOI: 10.1007/s00277-014-2084-2.

Shimoni A., Labopin M., Lorentino F., et al. Killer cell immunoglobulin-like receptor ligand mismatching and outcome after haploidentical transplantation with post-transplant cyclophosphamide. Leukemia. 2019; 33(1): 230–9. DOI: 10.1038/s41375-018-0170-5.

Ustun C., Brunstein C., DeFor T., et al. Importance of conditioning regimen intensity, MRD positivity, and KIR ligand mismatch in UCB transplantation. Bone Marrow Transplant. 2018; 53(1): 97–100. DOI: 10.1038/bmt.2017.212.

Solomon S.R., Aubrey M.T., Zhang X., et al. Selecting the best donor for haploidentical transplant: impact of HLA, killer cell immunoglobulin-like receptor genotyping, and other clinical variables. Biol Blood Marrow Transplant. 2018; 24(4): 789–98. DOI: 10.1016/j.bbmt.2018.01.013.

Arima N., Kanda J., Yabe T., et al. Increased relapse risk of acute lymphoid leukemia in homozygous HLA-C1 patients after HLA-matched allogeneic transplantation: A Japanese National Registry study. Biol Blood Marrow Transplant. 2020; 26(3): 431–7. DOI: 10.1016/j.bbmt.2019.10.032.

Arima N., Kanda J., Tanaka J., et al. Homozygous HLA-C1 is associated with reduced risk of relapse after HLA-matched transplantation in patients with myeloid leukemia. Biol Blood Marrow Transplant. 2018; 24(4): 717–25. DOI: 10.1016/j.bbmt.2017.11.029.

Oevermann L., Michaelis S.U., Mezger M., et al. KIR B haplotype donors confer a reduced risk for relapse after haploidentical transplantation in children with ALL. Blood. 2014; 124(17): 2744–7. DOI: 10.1182/blood-2014-03-565069.

Godal R., Bachanova V., Gleason M., et al. Natural killer cell killing of acute myelogenous leukemia and acute lymphoblastic leukemia blasts by killer cell immunoglobulin-like receptor-negative natural killer cells after NKG2A and LIR-1 blockade. Biol Blood Marrow Transplant. 2010; 16(5): 612–21. DOI: 10.1016/j.bbmt.2010.01.019.

Pérez‐Martínez A., Ferreras C., Pascual A., et al. Haploidentical transplantation in high‐risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH). Am J Hematol. 2020; 95(1): 28–37. DOI: 10.1002/ajh.25661.

Bao X., Wang M., Zhou H., et al. Donor killer immunoglobulin-like receptor profile Bx1 imparts a negative effect and centromeric B-specific gene motifs render a positive effect on standard-risk acute myeloid leukemia/myelodysplastic syndrome patient survival after unrelated donor hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2016; 22(2): 232–9. DOI: 10.1016/j.bbmt.2015.09.007.

Zhou H., Bao X., Wu X., et al. Donor selection for killer immunoglobulin-like receptors B haplotype of the centromeric motifs can improve the outcome after HLA-identical sibling hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014; 20(1): 98–105. DOI: 10.1016/j.bbmt.2013.10.017.

Babor F., Peters C., Manser A.R., et al. Presence of centromeric but absence of telomeric group B KIR haplotypes in stem cell donors improve leukaemia control after HSCT for childhood ALL. Bone Marrow Transplant. 2019; 54(11): 1847–58. DOI: 10.1038/s41409-019-0543-z.

Impola U., Turpeinen H., Alakulppi N., et al. Donor haplotype B of NK KIR receptor reduces the relapse risk in HLA-identical sibling hematopoietic stem cell transplantation of AML patients. Front Immunol. 2014; 5: 405. DOI: 10.3389/fimmu.2014.00405.

Tordai A., Bors A., Kiss K.P., et al. Donor KIR2DS1 reduces the risk of transplant related mortality in HLA-C2 positive young recipients with hematological malignancies treated by myeloablative conditioning. PLoS One. 2019; 14(6): e0218945. DOI: 10.1371/journal.pone.0218945.

Захарова В.В., Шеховцова Ж.Б., Шрагина О.А. и др. Влияние аллореактивности естественных киллерных клеток на эффективность аллогенной трансплантации гемопоэтических стволовых клеток с деплецией альфа/бетаTCR/CD19+ лимфоцитов у педиатрических пациентов с острыми лейкозами. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2018; 17(2): 39–50. DOI: 10.24287/1726-1708-2018-17-2-39-50.

Zakharova V.V., Shekhovtsova Z.B., Shragina O.A., et al. The influence of natural killer cell alloreactivity on the outcome of α/βTCR/CD19+ depleted allogeneic hematopoietic stem cell transplantation in pediatric patients with acute leukemia. Voprosi Gematologii/Onkologii i Immunopatologii v Pediatrii. 2018; 17(2): 39–50. DOI: 10.24287/1726-1708-2018-17-2-39-50. (In Russian).

Хамаганова Е.Г., Паровичникова Е.Н., Кузьмина Л.А. и др. Влияние генов киллерных иммуноглобулинподобных рецепторов и их HLA- лигандов на выживаемость больных острыми миелоидными лейкозами после трансплантации аллогенных гемопоэтических стволовых клеток. Гематология и трансфузиология. 2015; 60(3): 16–21.

Khamaganova E.G., Parovichnikova E.N., Kuzmina L.A., et al. Effect of killer immunoglobulin-like receptor genes and their HLA-ligands on the survival of patients with acute myeloid leukemia after transplantation of allogeneic hematopoietic stem cells. Gematologiya i Transfusiologiya. 2015; 60(3): 16–21. (In Russian).

Krieger E., Sabo R., Moezzi S., et al. Killer immunoglobulin-like receptor-ligand interactions predict clinical outcomes following unrelated donor transplantations. Biol Blood Marrow Transplant. 2020; 26(4): 672–82. DOI: 10.1016/j.bbmt.2019.10.016.

Choi I., Yoon S.R., Park S.-Y., et al. Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: A dose-escalation study. Biol Blood Marrow Transplant. 2014; 20(5): 696–704. DOI: 10.1016/j.bbmt.2014.01.031.

Song Y., Hu B., Liu Y., et al. IL-12/IL-18-preactivated donor NK cells enhance GVL effects and mitigate GvHD after allogeneic hematopoietic stem cell transplantation. Eur J Immunol. 2018; 48(4): 670–82. DOI: 10.1002/eji.201747177.

Ciurea S.O., Kongtim P., Soebbing D., et al. Decrease post-transplant relapse using donor-derived expanded NK-cells. Leukemia. 2022; 36(1): 155–64. DOI: 10.1038/s41375-021-01349-4.

Ijaz A., Khan A.Y., Malik S.U., et al. Significant risk of graft-versus-host disease with exposure to checkpoint inhibitors before and after allogeneic transplantation. Biol Blood Marrow Transplant. 2019; 25(1): 94–9. DOI: 10.1016/j.bbmt.2018.08.028.

Ruggeri L., Urbani E., André P., et al. Effects of anti-NKG2A antibody administration on leukemia and normal hematopoietic cells. Haematologica. 2016; 101(5): 626–33. DOI: 10.3324/haematol.2015.135301.

100

Hu L.J., Zhao X.Y., Yu X.X., et al. Quantity and quality reconstitution of NKG2A+ natural killer cells are associated with graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2019; 25(1): 1–11. DOI: 10.1016/j.bbmt.2018.08.008.

The authors declare that there are no conflicts of interest present.