TY - JOUR
T1 - Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia
AU - Costello, Régis T.
AU - Sivori, Simona
AU - Marcenaro, Emanuela
AU - Lafage-Pochitaloff, Marina
AU - Mozziconacci, Marie Joelle
AU - Reviron, Denis
AU - Gastaut, Jean Albert
AU - Pende, Daniela
AU - Olive, Daniel
AU - Moretta, Alessandro
PY - 2002/5/15
Y1 - 2002/5/15
N2 - The cytolytic function of natural killer (NK) cells is induced by the engagement of a series of activating receptors and coreceptors some of which have recently been identified and collectively termed natural cytotoxicity receptors (NCRs). Here, we analyzed the cytolytic function of NK cells obtained from patients with acute myeloid leukemia (AML). In sharp contrast with healthy donors, in most (16 of 18) patients with AML the majority of NK cells displayed low NCR surface density (NCRdull). This phenotype correlated with a weak cytolytic activity against autologous leukemic cells that could not be reversed by the monoclonal antibody-mediated disruption of HLA class I/killer immunoglobulinlike receptor interaction. The remaining 2 patients were characterized by NK cells having an NCRbright phenotype. Surprisingly, although displaying NCR-mediated cytolytic activity, these NCRbright NK cells were unable to kill autologous leukemic blasts. Importantly, the leukemic blasts from these 2 patients were also resistant to lysis mediated by normal NCRbright allogeneic NK cells. Our study suggests that in most instances the inability of NK cells to kill autologous leukemic blasts is consequent to low NCR surface expression. In few cases, however, this failure appears to involve a mechanism of tumor escape based on down-regulation of ligands relevant for NCR-mediated target cell recognition.
AB - The cytolytic function of natural killer (NK) cells is induced by the engagement of a series of activating receptors and coreceptors some of which have recently been identified and collectively termed natural cytotoxicity receptors (NCRs). Here, we analyzed the cytolytic function of NK cells obtained from patients with acute myeloid leukemia (AML). In sharp contrast with healthy donors, in most (16 of 18) patients with AML the majority of NK cells displayed low NCR surface density (NCRdull). This phenotype correlated with a weak cytolytic activity against autologous leukemic cells that could not be reversed by the monoclonal antibody-mediated disruption of HLA class I/killer immunoglobulinlike receptor interaction. The remaining 2 patients were characterized by NK cells having an NCRbright phenotype. Surprisingly, although displaying NCR-mediated cytolytic activity, these NCRbright NK cells were unable to kill autologous leukemic blasts. Importantly, the leukemic blasts from these 2 patients were also resistant to lysis mediated by normal NCRbright allogeneic NK cells. Our study suggests that in most instances the inability of NK cells to kill autologous leukemic blasts is consequent to low NCR surface expression. In few cases, however, this failure appears to involve a mechanism of tumor escape based on down-regulation of ligands relevant for NCR-mediated target cell recognition.
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U2 - 10.1182/blood.V99.10.3661
DO - 10.1182/blood.V99.10.3661
M3 - Article
C2 - 11986221
AN - SCOPUS:0037093066
VL - 99
SP - 3661
EP - 3667
JO - Blood
JF - Blood
SN - 0006-4971
IS - 10
ER -