Comprehensive analysis of NKG2D ligand expression and release in leukemia: implications for NKG2D-mediated NK cell responses.

Ligands of the prototypical activating NK receptor NKG2D render cancer cells susceptible to NK cell-mediated cytolysis if expressed at sufficiently high levels. However, malignant cells employ mechanisms to evade NKG2D-mediated immunosurveillance, such as NKG2D ligand (NKG2DL) shedding resulting in reduced surface expression levels. In addition, systemic downregulation of NKG2D on NK cells of cancer patients has been observed in many studies and was attributed to soluble NKG2DL (sNKG2DL), although there also are conflicting data.

The BCR/ABL-inhibitors imatinib, nilotinib and dasatinib differentially affect NK cell reactivity.

In chronic myeloid leukemia (CML), BCR/ABL-mediated oncogenic signaling can be targeted with the BCR/ABL-inhibitors Imatinib, Nilotinib and Dasatinib. However, these agents may also affect anti-tumor immunity. Here, we analyzed the effects of the 3 BCR/ABL-inhibitors on natural killer (NK) cell reactivity.