Analysis of the receptor-ligand interactions in the natural killer-mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: Evidence for the involvement of the Polio virus receptor (CD 155) and Nectin-2 (CD 112)

Daniela Pende, Grazia Maria Spaggiari, Stefania Marcenaro, Stefania Martini, Paola Rivera, Andrea Capobianco, Michela Falco, Edoardo Lanino, Ivana Pierri, Renato Zambello, Andrea Bacigalupo, Maria Cristina Mingari, Alessandro Moretta, Lorenzo Moretta

Research output: Contribution to journalArticle

Abstract

On the basis of recent clinical and experimental data, natural killer (NK) cells appear to play a crucial role in eradication of acute myeloid leukemias. In the present study, by exploiting our current knowledge on NK receptors and their ligands on target cells, we investigated the interactions between NK and leukemic cells. We show that the size of the NK cell subset expressing the killer immunoglobulin-like receptor (KIR) not engaged by the HLA-class I alleles of the patient parallels the degree of NK cytotoxicity against leukemic cells. A sharp down-regulation of HLA-class I molecules has been detected in various leukemias and it was more frequent in myeloid than in lymphoblastic leukemias. Analysis of the ligands for triggering NK receptors revealed the consistent expression of Poliovirus receptor (PVR) and Nectin-2 in myeloid leukemias. In contrast, major histocompatibility complex class I-related chain molecules A/B (MICA/B) and UL1b-binding protein (ULBPs) were either absent or weakly expressed. Accordingly, NK-mediated lysis of these leukemias was dependent on DNAM-1 but not NKG2D. The major role of NKp46 and NKp30 was also confirmed. The expression of PVR and/or Nectin-2 was less frequent in lymphoblastic leukemias. In most leukemias, both CD48 and NTBA were down-regulated. The correlation found between marker expression and susceptibility to lysis may reveal useful information for NK-based immunotherapy.

Original languageEnglish
Pages (from-to)2066-2073
Number of pages8
JournalBlood
Volume105
Issue number5
DOIs
Publication statusPublished - Mar 1 2005

ASJC Scopus subject areas

  • Hematology

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