The concept of tumor immunosurveillance has raised prospects for natural killer (NK) cell-based immunotherapy of human cancer. The cure of acute myeloid leukemia (AML) may depend on eradication of leukemic stem cells (LSCs), the self-renewing component of leukemia. Whether NK cells can recognize and lyse LSCs is not known. To develop strategies that effectively target AML-LSCs, we investigated anti-leukemic effects of human alloreactive single KIR(+) NK cells. NK effectors with KIR specificity mismatched with respect to HLA class I allotype of target cells effectively recognized AML-LSCs defined phenotypically as CD34(+)CD38(-), while healthy bone marrow-derived CD34(+)CD38(-) hematopoietic stem cells were spared, as demonstrated by cytotoxicity and hematopoietic colony-forming assays. The HDAC inhibitor valproic acid augmented the activating NKG2D ligand-dependent lysis of AML-CD34(+)CD38(-) LSCs. These results show that alloreactive NK cells have the potential to detect and target LSCs, and thus to improve the treatment outcome in AML.
Saturday, July 18, 2009
Alloreactive NK cells detect and target leukemic SCs
Human acute myeloid leukemia CD34+CD38– stem cells are susceptible to allorecognition and lysis by single KIR-expressing natural killer cells by Ulrich Langenkamp and 6 co-authors, including Aleksandra Wodnar-Filipowicz, Haematologica 2009(Jul 16) [Epub ahead of print][FriendFeed entry][Early version of the full text PDF]. PubMed Abstract: