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Donor and host coexpressing KIR ligands promote NK education after allogeneic hematopoietic stem cell transplantation
- Source :
- Blood Advances. 3:4312-4325
- Publication Year :
- 2019
- Publisher :
- American Society of Hematology, 2019.
-
Abstract
- The rate and extent of natural killer (NK)–cell education after hematopoietic cell transplantation correlates with leukemia control. To study the effect of donor and host HLA on NK-cell reconstitution, single killer-cell immunoglobulin-like receptor (KIR)+ NK cells (exhibiting KIR2DL1, KIR2DL2/KIR2DL3, or KIR3DL1 as their sole receptor) were grouped into 4 groups based on the interaction between donor/host HLA and donor inhibitory KIR in 2 cohorts (n = 114 and n = 276, respectively). On days 90 to 180 after transplantation, the absolute number and responsiveness against K562 cells (CD107a or interferon-γ expression) of single-KIR+ NK cells were higher in pairs where donor and host HLA both expressed ligands for donor inhibitory KIRs than in pairs where 1 or both of the donor and recipient HLA lacked at least 1 KIR ligand. NK-cell responsiveness was tuned commensurate with the number of inhibitory receptors from the donor. When both donor and host expressed the 3 major KIR ligands (HLA-C1, HLA-C2, and HLA-Bw4), NK cells expressing 3 inhibitory receptors (KIR2DL1/2DL3/3DL1) reached the maximum responsiveness against K562 cells compared with those NK cells expressing only 1 or 2 inhibitory receptors. When donor and host HLA both expressed all ligands for donor inhibitory KIRs, patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) showed the lowest recurrence rate after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). In conclusion, this study demonstrates that when both donors and hosts present all the KIR ligands for donor KIRs, reconstituted NK cells achieve better functional education and contribute to least relapse among patients. This observation study was registered at www.clinicaltrials.gov as #NCT02978274.
- Subjects :
- Adult
Male
Adolescent
Hematopoiesis and Stem Cells
medicine.medical_treatment
KIR Ligand
chemical and pharmacologic phenomena
Hematopoietic stem cell transplantation
Human leukocyte antigen
Biology
Ligands
Young Adult
Receptors, KIR
KIR2DL1
HLA Antigens
Recurrence
medicine
Humans
Histocompatibility Testing
Hematopoietic Stem Cell Transplantation
Myeloid leukemia
Hematology
Middle Aged
medicine.disease
Tissue Donors
Killer Cells, Natural
Transplantation
Leukemia
Treatment Outcome
Transplantation, Haploidentical
Cancer research
Female
KIR3DL1
Biomarkers
Subjects
Details
- ISSN :
- 24739537 and 24739529
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- Blood Advances
- Accession number :
- edsair.doi.dedup.....bf818d48254d3fa48e45e3e3b7e1017c