Acute myeloid leukemia (AML) cells induce, in vitro, NK cell abnormalities (NKCAs) including apoptosis and activating receptor down-regulation. The potential negative impact of AML cells on the therapeutic efficacy of NK cell-based strategies prompted us to analyze the mechanisms underlying NKCAs and to develop approaches to protect NK cells from NKCAs. NKCA induction by the AML leukemia cells target a subpopulation of peripheral blood NK cells and is interleukin-2 independent but is abrogated by a long-term culture of NK (LTNK) cells at 37°C. LTNK cells displayed a significantly enhanced ability to damage AML cells in vitro and inhibited the subcutaneous growth of ML-2 cells grafted into CB17 SCID mice. Actinomycin D restored the susceptibility of LTNK cells to NKCAs while TAPI-0, a functional analog of the tissue inhibitor of metalloproteinase (TIMP) 3, inhibits ML-2 cell-induced NKCAs suggesting that the generation of NK cell resistance to NKCAs involves RNA transcription and metalloproteinase (MPP) inactivation. This conclusion is supported by the reduced susceptibility to AML cell-induced NKCAs of LTNK cells in which TIMP3 gene and protein are over-expressed. This information may contribute to the rational design of targeted strategies to enhance the efficacy of NK cell-based-immunotherapy of AML with haploidentical NK cells.

Arriga, R., Caratelli, S., Coppola, A., Spagnoli, G.c., Venditti, A., Amadori, S., et al. (2016). Enhancement of anti-leukemia activity of NK cells in vitro and in vivo by inhibition of leukemia cell-induced NK cell damage. ONCOTARGET, 7(2), 2070-2079 [10.18632/oncotarget.6529].

Enhancement of anti-leukemia activity of NK cells in vitro and in vivo by inhibition of leukemia cell-induced NK cell damage

ARRIGA, ROBERTO;VENDITTI, ADRIANO;AMADORI, SERGIO;LAURO, DAVIDE;DEL PRINCIPE, MARIA ILARIA;BUCCISANO, FRANCESCO;CAPUANI, BARBARA;SCONOCCHIA, GIUSEPPE
2016

Abstract

Acute myeloid leukemia (AML) cells induce, in vitro, NK cell abnormalities (NKCAs) including apoptosis and activating receptor down-regulation. The potential negative impact of AML cells on the therapeutic efficacy of NK cell-based strategies prompted us to analyze the mechanisms underlying NKCAs and to develop approaches to protect NK cells from NKCAs. NKCA induction by the AML leukemia cells target a subpopulation of peripheral blood NK cells and is interleukin-2 independent but is abrogated by a long-term culture of NK (LTNK) cells at 37°C. LTNK cells displayed a significantly enhanced ability to damage AML cells in vitro and inhibited the subcutaneous growth of ML-2 cells grafted into CB17 SCID mice. Actinomycin D restored the susceptibility of LTNK cells to NKCAs while TAPI-0, a functional analog of the tissue inhibitor of metalloproteinase (TIMP) 3, inhibits ML-2 cell-induced NKCAs suggesting that the generation of NK cell resistance to NKCAs involves RNA transcription and metalloproteinase (MPP) inactivation. This conclusion is supported by the reduced susceptibility to AML cell-induced NKCAs of LTNK cells in which TIMP3 gene and protein are over-expressed. This information may contribute to the rational design of targeted strategies to enhance the efficacy of NK cell-based-immunotherapy of AML with haploidentical NK cells.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/13 - Endocrinologia
Settore MED/15 - Malattie del Sangue
eng
CD16; NK cell; NK cell abnormalities; TIMP3; acute myeloid leukemia
Arriga, R., Caratelli, S., Coppola, A., Spagnoli, G.c., Venditti, A., Amadori, S., et al. (2016). Enhancement of anti-leukemia activity of NK cells in vitro and in vivo by inhibition of leukemia cell-induced NK cell damage. ONCOTARGET, 7(2), 2070-2079 [10.18632/oncotarget.6529].
Arriga, R; Caratelli, S; Coppola, A; Spagnoli, G; Venditti, A; Amadori, S; Lanzilli, G; Lauro, D; Palomba, P; Sconocchia, T; DEL PRINCIPE, Mi; Maurillo, L; Buccisano, F; Capuani, B; Ferrone, S; Sconocchia, G
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/162183
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 9
social impact