Fig. 3: sMIC, not mMIC, induces the enhanced expression of pro-inflammatory cytokines and chemokines.

a, b NK cells isolated from Rag1−/− mice and cultured in presence of IL-2 for 5 days before co-culturing with tumor cell lines TC2, TC2-sMICB, and TC2-mMICB. The supernatant was collected from the 24 h co-culture for quantitative 31-plex mouse cytokine array assay (Eve Technologies). a Heatmap representing significantly higher levels of pro-inflammatory cytokines and chemokines produced by mouse NK cells when stimulated with sMICB compared to stimulation with mMICB. Heatmap data are represented as a percentage change in cytokine/chemokine levels produced by NK cells stimulated with sMICB and mMICB, respectively, versus NK cells stimulated with MIC negative control TC2 cells (baseline) and normalized to 0 to 1 scale. b Bar graphs showing differential levels of GM-CSF, CCL4, CCL3, and IL-10 produced by mouse NK cells when stimulated with sMICB vs. mMICB. Data points in the bar graph are mean values from two independent experiments. c, d Primary human NK cells were co-cultured tumor cell lines C1R, C1R-sMICA, and C1R-mMICA. The supernatant was collected from the 24 h co-culture for quantitative 42-plex human cytokine array analyses (Eve Technologies). c Heatmap representing significantly higher levels of pro-inflammatory cytokines and chemokines produced by human NK cells stimulated with sMICA compared to stimulation with mMICA. Heatmap data are represented as percentage changes in cytokine/chemokine levels produced by NK cells stimulated with sMICA and mMICA, respectively, versus NK cells stimulated with MIC negative control C1R cells (baseline) and normalized to 0 to 1 scale. d Bar graphs showing significantly higher levels of cytokines and chemokines IL-10, GM-CSF, CCL4, CCL3 in the culture supernatant of human NK cells stimulated with sMICA vs mMICA. Data shown are representative of three independent experiments. **P < 0.01, ***P < 0.001 with two-tailed Student’s t test.