Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell–dependent antitumor effects
J. Clin. Invest. Christophe Borg, et al. 114:379 doi:10.1172/JCI21102 [Go to this article.]

Figure 6
Correlation between NK cell activation and disease control in GIST patients. (A) Therapy with Gleevec-induced enhanced NK cell IFN-γ production. Blood NK cells were purified from GIST patients (Supplemental Table 1) at diagnosis after 2–12 months of therapy with 400 mg of Gleevec or from sex- and age-matched normal volunteers (NV) and cocultured with MD-DCs in the presence of LPS as described in Methods. Filled symbols correspond to individual patients or controls. Circles, objective responses; triangles; progressive disease. A longitudinal study enrolling 11 cases before and after Gleevec treatment is depicted with lines. Asterisk indicates significant differences between mean values of IFN-γ production after Gleevec compared with prior Gleevec or controls (P < 0.05) in 37 consecutive patients. (B) Correlation between clinical outcome and NK cell activation induced by therapy with Gleevec. The clinical responders exhibited stable disease, or partial or complete regressions (WHO criteria). The biological responders exhibited NK cell IFN-γ secretion above 130 pg/ml after at least 2 months of Gleevec therapy (cut-off defined according to the data shown in A). A significant correlation between NK cell activation and clinical outcome at the time of NK cell activation assessment was found (**P = 0.03, Fisher’s exact method). (C) NK cell activation is associated with prolonged time to progression in GIST patients treated with Gleevec. The study of the time to progression was performed for 43 patients with a median follow-up of 13.2 months. Patients who exhibited enhanced NK cell functions at 2 months of Gleevec (n = 22; red) and those who did not (n = 21; blue) (log rank test, P = 0.03).