Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia

Régis T. Costello, Simona Sivori, Emanuela Marcenaro, Marina Lafage-Pochitaloff, Marie Joelle Mozziconacci, Denis Reviron, Jean Albert Gastaut, Daniela Pende, Daniel Olive, Alessandro Moretta

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)3661-3667
Number of pages7
JournalBlood
Volume99
Issue number10
DOIs
Publication statusPublished - May 15 2002

ASJC Scopus subject areas

  • Hematology

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