GISTs are NK cell–sensitive targets. (A) NK cell recognition of a GIST cell line. CD3^–/CD56⁺ NK cells from GIST patients at diagnosis were activated overnight with 1000 IU rhuIL-2. The cytolytic activity of these NK cells was tested against the NK cell-–sensitive K562 targets and against a GIST cell line in a ⁵¹Cr release assay, using an E/T ratio of 10:1. Data represent the means of triplicate wells of 7 different GIST patients. Each symbol represents an individual patient’s NK cell lysis of both targets (see key in B). (B) Gleevec promoted enhanced NK cell recognition of GIST cells. Experimental settings were the same as in A, but cytotoxicity assays had been performed before and 2 months after initiation of Gleevec therapy. (C) DC/NK cell cross-talk in a Gleevec-induced lichenoid dermatitis. Skin biopsies from a lichenoid dermatitis were taken from a patient bearing GISTs in complete regression after a year of oral administration of Gleevec. Formol-fixed and paraffin-embedded sections (4 μm thick) were immunohistochemically stained with an anti-DC-LAMP mAb (Schering-Plough Corp., Dardilly, France) and anti-CD57 mAb (NK1, Dako A/S, Glostrup, Denmark). Double-staining with anti-CD3 and anti-CD57 mAb demonstrated that CD57⁺ cells were all CD3^–. DC-LAMP⁺ mature dendritic cells were visualized by light microscope (brown staining). CD57⁺ NK cells (3 black boxes) were identified by their red color and visible nuclei (×400 magnification).