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).
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.
Pende
Daniela
D
Istituto Nazionale per la Ricerca sul Cancro, L.go R. Benzi 10, 16132 Genova, Italy. daniela.pende@istge.it
Spaggiari
Grazia Maria
GM
Marcenaro
Stefania
S
Martini
Stefania
S
Rivera
Paola
P
Capobianco
Andrea
A
Falco
Michela
M
Lanino
Edoardo
E
Pierri
Ivana
I
Zambello
Renato
R
Bacigalupo
Andrea
A
Mingari
Maria Cristina
MC
Moretta
Alessandro
A
Moretta
Lorenzo
L
D002450:Cell Communication; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D053646:Interleukin-2 Receptor beta Subunit; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology*; D007945:Leukemia, Lymphoid / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000473:pathology*; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D054340:Receptors, KIR; D011991:Receptors, Virus / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; C508020:IL2RB protein, human; D053646:Interleukin-2 Receptor beta Subunit; D008024:Ligands; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018123:Receptors, Interleukin; D054340:Receptors, KIR; D011991:Receptors, Virus; C066100:poliovirus receptor