Natural Killer Cells Significantly Target and Eliminate Chronic Myelogenous Leukemia via Direct Cytotoxicity or Antibody-Dependent Cellular Cytotoxicity.

This study was conducted to investigate whether natural killer (NK) cells can kill and/or inhibit the tumor growth of hematological tumors. When K562, the chronic myeloid leukemia cell line, was treated with the culture media collected from interleukin-2 (IL-2) and anti-CD16 mAbs-treated NK cells, increased surface expression levels of differentiation antigens MHC-class I, CD54, and PD-L1 were observed on K562. This finding validated our previous reports demonstrating that the NK cells induce tumor differentiation via their secreted factors. Next, we investigated NK cell-mediated cytotoxicity against stem-like and differentiated K562, and observed that increased NK cells induced direct cytotoxicity in stem-like K562 compared with differentiated K562. Upon differentiation, tumors become resistant to direct NK cell-mediated cytotoxicity, but were lysed by NK cells via antibody-dependent cellular cytotoxicity (ADCC). NK cell-mediated ADCC was observed when K562 cells were treated with anti-PD-L1. Thus, primary NK cells, although they cannot induce direct lysis in differentiated tumors, can target them via ADCC.