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Dynamic Changes of Inhibitory Killer-Immunoglobulin-Like Receptors on NK Cells after Allogeneic Hematopoietic Stem Cell Transplantation: An Initial Study

T. Dekojová, L. Houdová, J. Fatka, P. Pitule, P. Ostašov, VS. Caputo, H. Gmucová, D. Lysák, P. Jindra, M. Holubová,

. 2020 ; 9 (11) : . [pub] 20201029

Language English Country Switzerland

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc21001870

Grant support
NV18-03-00277 Ministerstvo Zdravotnictví Ceské Republiky

Killer-immunoglobulin-like receptors (KIRs) are critical natural killer (NK) cell regulators. The expression of KIRs is a dynamic process influenced by many factors. Their ligands-HLA(Human Leukocyte Antigen) class I molecules-are expressed on all nucleated cells that keep NK cells under control. In hematopoietic stem cell transplantation (HSCT), NK cells play an essential role in relapse protection. In the presented pilot study, we characterized the dynamic expression of inhibitory KIRS (iKIRs), which protect cells against untoward lysis, in donors and patients during the first three months after HSCT using flow cytometry. The expression of all iKIRs was highly variable and sometimes correlated with patients' clinical presentation and therapy regiment. Cyclophosphamide (Cy) in the graft-versus-host disease (GvHD) prevention protocol downregulated KIR2DL1 to just 25% of the original donor value, and the FEAM (Fludarabine + Etoposid + Ara-C + Melphalan) conditioning protocol reduced KIR2DL3. In lymphoid neoplasms, there was a slightly increased KIR2DL3 expression compared to myeloid malignancies. Additionally, we showed that the ex vivo activation of NK cells did not alter the level of iKIRs. Our study shows the influence of pre- and post-transplantation protocols on iKIR expression on the surface of NK cells and the importance of monitoring their cell surface.

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$a Dekojová, Tereza $u Department of Haematology and Oncology, University Hospital Pilsen, 304 60 Pilsen, Czech Republic. Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University, 301 66 Pilsen, Czech Republic. $7 xx0313012
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$a Killer-immunoglobulin-like receptors (KIRs) are critical natural killer (NK) cell regulators. The expression of KIRs is a dynamic process influenced by many factors. Their ligands-HLA(Human Leukocyte Antigen) class I molecules-are expressed on all nucleated cells that keep NK cells under control. In hematopoietic stem cell transplantation (HSCT), NK cells play an essential role in relapse protection. In the presented pilot study, we characterized the dynamic expression of inhibitory KIRS (iKIRs), which protect cells against untoward lysis, in donors and patients during the first three months after HSCT using flow cytometry. The expression of all iKIRs was highly variable and sometimes correlated with patients' clinical presentation and therapy regiment. Cyclophosphamide (Cy) in the graft-versus-host disease (GvHD) prevention protocol downregulated KIR2DL1 to just 25% of the original donor value, and the FEAM (Fludarabine + Etoposid + Ara-C + Melphalan) conditioning protocol reduced KIR2DL3. In lymphoid neoplasms, there was a slightly increased KIR2DL3 expression compared to myeloid malignancies. Additionally, we showed that the ex vivo activation of NK cells did not alter the level of iKIRs. Our study shows the influence of pre- and post-transplantation protocols on iKIR expression on the surface of NK cells and the importance of monitoring their cell surface.
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$a Houdová, Lucie $u NTIS, Faculty of Applied Science, University of West Bohemia, 301 00 Pilsen, Czech Republic.
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$a Fatka, Jiří $u NTIS, Faculty of Applied Science, University of West Bohemia, 301 00 Pilsen, Czech Republic.
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$a Pitule, Pavel $u Department of Haematology and Oncology, University Hospital Pilsen, 304 60 Pilsen, Czech Republic. Laboratory of Tumor Biology and Immunotherapy, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic.
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$a Ostašov, Pavel $u Laboratory of Tumor Biology and Immunotherapy, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic.
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$a Caputo, Valentina S $u Department of Immunology and Inflammation, Faculty of Medicine, Imperial College London, London W12 0NN, UK.
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$a Gmucová, Hana $u Department of Haematology and Oncology, University Hospital Pilsen, 304 60 Pilsen, Czech Republic.
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$a Lysák, Daniel $u Department of Haematology and Oncology, University Hospital Pilsen, 304 60 Pilsen, Czech Republic.
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$a Jindra, Pavel $u Department of Haematology and Oncology, University Hospital Pilsen, 304 60 Pilsen, Czech Republic.
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$a Holubová, Monika $u Department of Haematology and Oncology, University Hospital Pilsen, 304 60 Pilsen, Czech Republic. Laboratory of Tumor Biology and Immunotherapy, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, 323 00 Pilsen, Czech Republic.
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