Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Arriga, R; Caratelli, S; Coppola, A; Spagnoli, GC; 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.
Enhancement of anti-leukemia activity of NK cells in vitro and in vivo by inhibition of leukemia cell-induced NK cell damage.
Oncotarget. 2016; 7(2): 2070-2079.
Doi: 10.18632/oncotarget.6529
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- Co-Autor*innen der Med Uni Graz
- Sconocchia Tommaso
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antineoplastic Agents - pharmacology
- Apoptosis - drug effects
- Biomarkers, Tumor - genetics
- Biomarkers, Tumor - metabolism
- Cell Proliferation - drug effects
- Gene Expression Regulation, Neoplastic - drug effects
- Humans -
- In Vitro Techniques -
- Killer Cells, Natural - immunology
- Killer Cells, Natural - metabolism
- Killer Cells, Natural - pathology
- Leukemia, Myeloid, Acute - immunology
- Leukemia, Myeloid, Acute - metabolism
- Leukemia, Myeloid, Acute - prevention & control
- Lymphocytes - immunology
- Lymphocytes - metabolism
- Lymphocytes - pathology
- Male -
- Mice -
- Mice, SCID -
- RNA, Messenger - genetics
- Real-Time Polymerase Chain Reaction -
- Reverse Transcriptase Polymerase Chain Reaction -
- Tumor Cells, Cultured -
- Find related publications in this database (Keywords)
- NK cell
- acute myeloid leukemia
- CD16
- TIMP3
- NK cell abnormalities