Role of NK cell receptors in allogeneic stem cell transplantation in patients with acute myeloid leukaemia
Authors:
A. Machuldová 1,2; P. Pitule 1,2; T. Dekojová 2,3; P. Jindra 3; M. Holubová 1,3
Authors‘ workplace:
Laboratoř nádorové bio logie a imunoterapie, Biomedicínské centrum LF UK v Plzni
1; Ústav histologie a embryologie, LF UK v Plzni
2; Hematologicko-onkologické oddělení, FN Plzeň
3
Published in:
Transfuze Hematol. dnes,29, 2023, No. 4, p. 219-226.
Category:
Review/Educational Papers
doi:
https://doi.org/10.48095/cctahd2023prolekare.cz17
Overview
NK cells play an important role in allogeneic stem cell transplantation; not only as effector cells in the eradication of remaining cancer cells but also as potential inducers of graft versus host disease. Hence, it is important to understand their regulation and how the patient’s immune system affects donor NK cells. NK cell inhibition or activation is directed by many receptors which interact with a broad spectrum of ligands. Inhibition ligands signal that the target cell is healthy, and activating ligands reflect that the cell is damaged. The most investigated receptors are KIR together with the NKG2D receptor with its ligands MICA and MICB. This work describes their role in stem cell transplantation.
Keywords:
acute myeloid leukemia – KIR – NKG2D – MICA – MICB
Sources
1. Vakiti A, Mewawalla P. Acute myeloid leukemia. In: StatPearls. edn. Treasure Island (FL): StatPearls Publishing 2022.
2. Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM. Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges. Blood Rev. 2019; 36: 70–87.
3. Loke J, Buka R, Craddock C. Allogeneic stem cell transplantation for acute myeloid leukemia: who, when, and how? Front Immunol. 2021; 12: 659595.
4. Giralt S, Bishop MR. Principles and overview of allogeneic hematopoietic stem cell transplantation. In., edn.: Springer US. 2009; 1–21.
5. Paczulla AM, Rothfelder K, Raffel S, et al. Publisher Correction: Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion. Nature. 2019; 572 (7770): E19.
6. Bertaina A, Andreani M. Major histocompatibility complex and hematopoietic stem cell transplantation: beyond the classical HLA polymorphism. Int J Mol Sci. 2018; 19 (2): 621.
7. Horowitz A, Stegmann KA, Riley EM. Activation of natural killer cells during microbial infections. Front Immunol. 2011; 2: 88.
8. Simonetta F, Alvarez M, Negrin RS. Natural killer cells in graft-versus-host-disease after allogeneic hematopoietic cell transplantation. Front Immunol. 2017; 8: 465.
9. Olson JA, Leveson-Gower DB, Gill S, Baker J, Beilhack A, Negrin RS. NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects. Blood. 2010; 115 (21): 4293–4301.
10. Boudreau JE, Hsu KC. Natural killer cell education and the response to infection and cancer therapy: stay tuned. Trends Immunol. 2018; 39 (3): 222–239.
11. Sivori S, Vacca P, Del Zotto G, Munari E, Mingari MC, Moretta L. Human NK cells: surface receptors, inhibitory checkpoints, and translational applications. Cell Mol Immunol. 2019; 16 (5): 430–441.
12. Zingoni A, Cecere F, Vulpis E, et al. Genotoxic stress induces senescence-associated ADAM10-dependent release of NKG2D MIC ligands in multiple myeloma cells. J Immunol. 2015; 195 (2): 736–748.
13. Long EO, Colonna M, Lanier LL. Inhibitory MHC class I receptors on NK and T cells: a standard nomenclature. Immunol Today. 1996; 17 (2): 100.
14. Margolis DJ, Mitra N, Hoffstad OJ, et al. Association of KIR2DL5, KIR2DS5, and KIR2DS1 allelic variation and atopic dermatitis. Scient Rep. 2023; 13 (1): 1730.
15. Robinson J, Halliwell JA, Hayhurst JD, Flicek P, Parham P, Marsh SG. The IPD and IMGT/HLA database: allele variant databases. Nucleic Acids Res. 2015; 43 (Database issue): D423–D431.
16. Dębska-Zielkowska J, Moszkowska G, Zieliński M, et al. KIR receptors as key regulators of NK cells activity in health and disease. Cells. 2021; 10 (7): 1777.
17. Hsu KC, Liu XR, Selvakumar A, Mickelson E, O‘Reilly RJ, Dupont B. Killer Ig-like receptor haplotype analysis by gene content: evidence for genomic diversity with a minimum of six basic framework haplotypes, each with multiple subsets. J Immunol. 2002; 169 (9): 5118–5129.
18. Robinson J, Barker DJ, Georgiou X, Cooper MA, Flicek P, Marsh SGE. IPD-IMGT/HLA database. Nucleic Acids Res. 2020; 48 (D1): D948–D955.
19. Goodridge JP, Lathbury LJ, Steiner NK, et al. Three common alleles of KIR2DL4 (CD158d) encode constitutively expressed, inducible and secreted receptors in NK cells. Eur J Immunol. 2007; 37 (1): 199–211.
20. VandenBussche CJ, Dakshanamurthy S, Posch PE, Hurley CK. A single polymorphism disrupts the killer Ig-like receptor 2DL2/2DL3 D1 domain. J Immunol. 2006; 177 (8): 5347–5357.
21. Pando MJ, Gardiner CM, Gleimer M, McQueen KL, Parham P. The protein made from a common allele of KIR3DL1 (3DL1*004) is poorly expressed at cell surfaces due to substitution at positions 86 in Ig domain 0 and 182 in Ig domain 1. J Immunol. 2003; 171 (12): 6640–6649.
22. Gardiner CM, Guethlein LA, Shilling HG, et al. Different NK cell surface phenotypes defined by the DX9 antibody are due to KIR3DL1 gene polymorphism. J Immunol. 2001; 166 (5): 2992–3001.
23. Carr WH, Pando MJ, Parham P. KIR3DL1 polymorphisms that affect NK cell inhibition by HLA-Bw4 ligand. J Immunol. 2005; 175 (8): 5222–5229.
24. 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.
25. Cooley S, Trachtenberg E, Bergemann TL, 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): 726–732.
26. Shaffer BC, Hsu KC. How important is NK alloreactivity and KIR in allogeneic transplantation? Best Pract Res Clin Haematol. 2016; 29 (4): 351–358.
27. Bari R, Rujkijyanont P, Sullivan E, et al. Effect of donor KIR2DL1 allelic polymorphism on the outcome of pediatric allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2013; 31 (30): 3782–3790.
28. Bari R, Bell T, Leung WH, et at. Significant functional heterogeneity among KIR2DL1 alleles and a pivotal role of arginine 245. Blood. 2009; 114 (25): 5182–5190.
29. Boudreau JE, Giglio F, Gooley TA, et al. KIR3DL1/HLA-B subtypes govern acute myelogenous leukemia relapse after hematopoietic cell transplantation. J Clin Oncol. 2017; 35 (20): 2268–2278.
30. Shaffer BC, Heller G, Le Luduec J-B, et al. Selection of unrelated allogeneic hematopoietic cell donors based on KIR3DL1 allotypes is feasible and results in improved disease-free survival in transplant recipients with MDS and AML. Blood. 2016; 128 (22): 990–990.
31. Shaffer BC, Le Luduec J-B, Park S, et al. Prospective KIR genotype evaluation of hematopoietic cell donors is feasible with potential to benefit patients with AML. Blood Adv. 2021; 5 (7): 2003–2011.
32. Dubreuil L, Maniangou B, Chevallier P, et al. Centromeric KIR AA individuals harbor particular KIR alleles conferring beneficial NK cell features with implications in haplo-identical hematopoietic stem cell transplantation. Cancers (Basel). 2020; 12 (12): 3595.
33. Heidenreich S, Kröger N. Reduction of relapse after unrelated donor stem cell transplantation by KIR-based graft selection. Front Immunol. 2017; 8: 41.
34. Symons HJ, Fuchs EJ: Hematopoietic SCT from partially HLA-mismatched (HLA-haploidentical) related donors. Bone Marrow Transplant. 2008; 42 (6): 365–377.
35. 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): 433–440.
36. Chewning JH, Gudme CN, Hsu KC, Selvakumar A, Dupont B. KIR2DS1-positive NK cells mediate alloresponse against the C2 HLA-KIR ligand group in vitro. J Immunol. 2007; 179 (2): 854–868.
37. 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. Blood. 2005; 105 (12): 4878–4884.
38. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002; 295 (5562): 2097–2100.
39. 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): 814–819.
40. Beelen DW, Ottinger HD, Ferencik S, et al. Genotypic inhibitory killer immunoglobulin-like receptor ligand incompatibility enhances the long-term antileukemic effect of unmodified allogeneic hematopoietic stem cell transplantation in patients with myeloid leukemias. Blood. 2005; 105 (6): 2594–2600.
41. Bornhäuser M, Schwerdtfeger R, Martin H, Frank KH, Theuser C, Ehninger G. Role of KIR ligand incompatibility in hematopoietic stem cell transplantation using unrelated donors. Blood. 2004; 103 (7): 2860–2861; author reply 2862.
42. Verheyden S, Schots R, Duquet W, Demanet C. A defined donor activating natural killer cell receptor genotype protects against leukemic relapse after related HLA-identical hematopoietic stem cell transplantation. Leukemia. 2005; 19 (8): 1446–1451.
43. Borrego F, Masilamani M, Marusina AI, Tang X, Coligan JE. The CD94/NKG2 family of receptors: from molecules and cells to clinical relevance. Immunol Res. 2006; 35 (3): 263–278.
44. Kim DK, Kabat J, Borrego F, Sanni TB, You CH, Coligan JE. Human NKG2F is expressed and can associate with DAP12. Mol Immunol. 2004; 41 (1): 53–62.
45. Orbelyan GA, Tang F, Sally B, et al. Human NKG2E is expressed and forms an intracytoplasmic complex with CD94 and DAP12. J Immunol. 2014; 193 (2): 610–616.
46. Lanier LL, Corliss B, Wu J, Phillips JH. Association of DAP12 with activating CD94/NKG2C NK cell receptors. Immunity. 1998; 8 (6): 693–701.
47. Bellón T, Heredia AB, Llano M, et al. Triggering of effector functions on a CD8+ T cell clone upon the aggregation of an activatory CD94/kp39 heterodimer. J Immunol. 1999; 162 (7): 3996–4002.
48. Creelan BC, Antonia SJ. The NKG2A immune checkpoint – a new direction in cancer immunotherapy. Nature Rev Clin Oncol. 2019; 16 (5): 277–278.
49. Machuldova A, Holubova M, Caputo VS, et al. Role of polymorphisms of NKG2D receptor and its ligands in acute myeloid leukemia and human stem cell transplantation. Front Immunol. 2021; 12: 651751.
50. Hayashi T, Imai K, Morishita Y, Hayashi I, Kusunoki Y, Nakachi K. Identification of the NKG2D haplotypes associated with natural cytotoxic activity of peripheral blood lymphocytes and cancer immunosurveillance. Cancer Res. 2006; 66 (1): 563–570.
51. Espinoza JL, Takami A, Onizuka M, et al. NKG2D gene polymorphism has a significant impact on transplant outcomes after HLA-fully-matched unrelated bone marrow transplantation for standard risk hematologic malignancies. Haematologica 2009; 94 (10): 1427.
52. Machuldova A, Houdova L, Kratochvilova K, et al. Single-nucleotide polymorphisms in MICA and MICB genes could play a role in the outcome in AML patients after HSCT. J Clin Med. 2021; 10 (20): 4636.
53. Eagle RA, Jafferji I, Barrow AD. Beyond stressed self: evidence for NKG2D ligand expression on healthy cells. Curr Immunol Rev. 2009; 5 (1): 22–34.
54. Stephens HA. MICA and MICB genes: can the enigma of their polymorphism be resolved? Trends Immunol. 2001; 22 (7): 378–385.
55. Pérez-Rodríguez M, Argüello JR, Fischer G, et al. Further polymorphism of the MICA gene. Eur J Immunogenet. 2002; 29 (1): 35–46.
56. Bahram S. MIC genes: from genetics to biology. Adv Immunol. 2000; 76: 1–60.
57. Carapito R, Jung N, Kwemou M, et al. Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD. Blood. 2016; 128 (15): 1979–1986.
58. Parmar S, Del Lima M, Zou Y, et al. Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease. Blood. 2009; 114 (14): 2884–2887.
59. Fuerst D, Neuchel C, Niederwieser D, et al. Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation. Blood. 2016; 128 (26): 3169–3176.
60. Abdelhakim H, Abdel-Azim H, Saad A. Role of ab T cell depletion in prevention of graft versus host disease. Biomedicines. 2017; 5 (3): 35.
61. Isernhagen A, Malzahn D, Viktorova E, et al. The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation. EMBO Mol Med. 2015; 7 (11): 1480–1502.
62. Boukouaci W, Busson M, Peffault de Latour R, et al: MICA-129 genotype, soluble MICA, and anti-MICA antibodies as biomarkers of chronic graft-versus-host disease. Blood. 2009; 114 (25): 5216–5224.
63. Carapito R, Aouadi I, Pichot A, et al. Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus-host disease in conjunction with the CMV status. Bone Marrow Transplant. 2020; 55 (7): 1367–1378.
Labels
Haematology Internal medicine Clinical oncologyArticle was published in
Transfusion and Haematology Today
2023 Issue 4
Most read in this issue
- What is new in the treatment of peripheral T-cell lymphomas in the Czech Republic
- Role of NK cell receptors in allogeneic stem cell transplantation in patients with acute myeloid leukaemia
- Do we need a system for sharing spare blood products?