KIR genotype distribution among patients with multiple myeloma: Higher prevalence of KIR 2DS4 and KIR 2DS5 genes

Abstract

IntroductionNatural killer (NK) cells possess an antitumor activity against multiple myeloma cells proven by the susceptibility of plasmocytes to NK lysis. In the early stage of MM, the killing of MM cells is mediated by natural cytotoxicity receptors (NRC) and NKG2D-dependent pathway, while in the late stage, NK cells lose their killing potential against MM cells due to the high expression of HLA class I molecules on MM cells.AimThe aim of this paper is to study KIR expression of NK cells in MM patients and in healthy controls, to check for any association between KIR genotypes and MM.MethodsKIR genotype was analyzed in 120 healthy Lebanese individuals and 34 MM patients using the KIR Genotyping SSP kit.ResultsKIR 2DS4*001/002 and KIR 2DS5 were found to be significantly more prevalent among MM patients as compared to controls. For MM patients, the AA, AB, and BB genotype frequencies were, respectively, 38.23%, 47.06% and 14.71% with an A:B ratio of 1.62:1. As for the healthy controls, the AA, AB, and BB genotype frequencies were, respectively, 39.17%, 50%, and 10.83% with an A:B ratio of 1.80:1.ConclusionThe interesting observation of the significant presence of KIR2DS4 and KIR2DS5 genes more among multiple myeloma patients than controls is worth further clinical, translational as well as survival research studies in these cases.

Natural killer cells in patients with hematologic malignancies, solid tumors and in recipients of hematopoietic stem cell transplantation

“…Examples of non-speci ic adoptive immunotherapies include: CD3/CD28-activated DLIs; lymphokine-activated killer cells; anti-CD3-activated killer cells; tumor-in iltrating lymphocytes; in vitro-generated or selected tumor cytotoxic T lymphocytes; γ/δ-T cells; and NK cells [26]. However, NK cells are attractive candidates for adoptive cellular therapy in patients with HMs and solid tumors, as well as in recipients of allogeneic HSCT as they enhance GVT/GVL effects without causing GVHD [1,26,97,[169][170][171][172][173][174].…”

“…MM cells exhibit speci ic immunoevasive strategies in order to circumvent and attenuate NK cell function [176]. Transformed plasma cells in MM are susceptible to NK cell-mediated killing by engagement of tumor ligands for activating receptors or missing self-recognition [174][175][176]. Despite the advancements in novel therapies and autologous HSCT, MM remains an incurable and dif icult-to-treat HM due to drug resistance predisposed to by the immunosuppressive microenvironment and clonal evolution which favor disease progression [175].…”

Natural killer cell immunotherapy against multiple myeloma: Progress and possibilities

“…Myeloma cells employ various mechanisms to escape from NK cell innate immune‐mediated destruction. With the progression of disease, myeloma cells upregulate the expression of the HLA class I molecules to reduce the NK cell sensitivity . In the later stage, myeloma cells shed the soluble NKG2DLs, resulting in drug resistance for NKG2D‐mediated killing .…”

“…32,33 Surprisingly, more to reduce the NK cell sensitivity. 36,37 In the later stage, myeloma cells shed the soluble NKG2DLs, resulting in drug resistance for NKG2Dmediated killing. 38,39 In addition, NK cells derived from patients with MM highly express PD-1, which binds to PD-L1 on myeloma cell surface and disables the immune cells' antitumor response.…”

Killer cell immunoglobulin-like receptors in immune thrombocytopenia

“…, scleroderma 82 , multiple sclerosis 83,84 , pre-eclampsia 85 , resistance to HIV 86,87 and HCV viral infection 88 , coronary artery disease, and melanoma 89 . In haematological conditions, KIR genotype associations have been seen in allogeneic and autologous stem cell transplantation 90,91 , risk for relapse in paediatric acute lymphoblastic leukaemia (ALL) 92 , chronic myeloid leukaemia (CML) and response to tyrosine kinase inhibitors (TKI) 93,94 and incidence of plasma cell myeloma 95 . It is likely that there is disease modification by specific KIR-ligand interactions rather than by global T-cell or NK cell responsiveness 87 .…”