Early evaluation of natural killer activity in post-transplant acute myeloid leukemia patients.
The focus of this study was to investigate NK cell reconstitution early after hematopoietic stem cell transplantation (HSCT). We were particularly interested in acute myeloid leukemia (AML) since patients with this disease may display an altered NK cell function. The function and the phenotype of donor-derived NK cells obtained from 35 allografted patients 30 and 60 days after HSCT for AML or other-than-AML hematological malignancies has been assessed. NK functional status was investigated by measuring the degranulation capacity (externalization of CD107a) of NK cells against human K562. We also concomitantly determined the concentration of selected cytokines known to modulate NK function and/or receptor expression. At day 30, donor-derived AML and non-AML NK cells could efficiently degranulate when exposed to leukemic K562 targets. At day 60, we observed a reduced NK degranulation potential in AML patients only. Decreased NK activity in AML patients was concomitant to NKp46 and NKp30 down-regulation. AML NK cells were chronically exposed to low IL-2 levels following HSCT. TGF-beta(1) was undetectable in all patients. In AML, the functional activity of donor-derived NK cells is remarkable at day 30 but may strongly decrease two months after HSCT. Therefore, in this condition, early NK immune-modulation might improve HSCT outcome.
Pittari
G
G
INSERM U753, Institut Gustave Roussy, Villejuif, France.
Fregni
G
G
Roguet
L
L
Garcia
A
A
Vataire
A-L
AL
Wittnebel
S
S
Amsellem
S
S
Chouaib
S
S
Bourhis
J-H
JH
Caignard
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014019:Tissue Donors; D016896:Treatment Outcome; D055815:Young Adult