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 Poliovirus receptor (CD155) and Nectin-2 (CD112)

Blood - Tập 105 Số 5 - Trang 2066-2073 - 2005
Daniela Pende1, Grazia Maria Spaggiari1, Stefania Marcenaro1, Stefania Martini1, Paola Andrea Rivera1, Andrea Capobianco1, Michela Falco1, Edoardo Lanino1, Ivana Pierri1, Renato Zambello1, Andrea Bacigalupo1, Maria Cristina Mingari1, Alessandro Moretta1, Lorenzo Moretta1
1From the Istituto Nazionale per la Ricerca sul Cancro; DIMES, Centro di Eccellenza per la Ricerca Biomedica, UO Ematologia, and DOBIG, Università di Genova; Laboratorio di Immunologia and Dipartimento di Ematologia e Oncologia Pediatrica, Istituto Giannina Gaslini; Divisione di Ematologia II, Ospedale San Martino, Genova, Italy; and Dipartimento di Medicina Clinica e Sperimentale, Ematologia e Immunologia Clinica, Università di Padova, Padova, Italy.

Tóm tắt

AbstractOn 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.

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Tài liệu tham khảo

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Blood

Tập 105 Số 5

2066-2073

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