AI Article Synopsis
- Acute myeloid leukemia (AML) cells negatively affect natural killer (NK) cells by causing abnormalities such as apoptosis and reducing activating receptors, which could reduce the effectiveness of NK cell therapies.
- The study found that long-term cultured NK cells (LTNK) can resist these abnormalities and exhibit improved ability to attack AML cells both in lab conditions and in mouse models.
- Enhancing the resistance of NK cells to AML-induced abnormalities involves both RNA transcription and the inhibition of certain proteins, indicating a potential pathway to improve NK cell-based immunotherapies against AML.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811516 | PMC |
| http://dx.doi.org/10.18632/oncotarget.6529 | DOI Listing |
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