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. 2013 Jun 10;8(6):e66825. doi: 10.1371/journal.pone.0066825

Figure 3. MYXV-enhanced NK cell-mediated clearance of U87 tumor results in prolonged survival.

Figure 3

(A) Bioluminescence imaging (BLI) to monitor growth of orthotopic luciferase-expressing human U87 xenografts in CB-17 SCID mice. A total of 1.5×105 IL-2-activated NK cells were administered intratumorally, 48 h (day 24 post tumor implantation) following intratumoral MYXV treatment (5×106 ffu/mouse, day 22 post tumor implantation); PBS =  phosphate-buffered saline. A heat map indicating tumor size in 4 to 5 mice in each group is shown. (B) Luminescent intensities from U87 xenografts were quantified on day 0, 7 and 14 post-treatment (day 22, 29, and 36 post tumor implantation respectively) to monitor tumor clearance. Results show the mean fold-increase in tumor size after treatment (calculated as luminescent intensity on day 22/day 22, day 29/day 22, day 36/day 22 post tumor implantation). A statistically significant reduction in tumor size was observed in the MYXV+NK group compared with the other groups, 14 days post-treatment (36 days post tumor implantation, NK vs. MYXV+NK: 6.58±1.34 vs. 0.33±0.09 fold increase, difference = 6.25±1.34, 95% CI = 3.153 to 9.350, P1 = .0016; MYXV vs. MYXV+NK: 3.96±1.35 vs. 0.33±0.09 fold increase, difference = 3.63±1.35, 95% CI = 0.5121 to 6.750, P2 = .0277). Also, 7 days post-treatment (29 days post tumor implantation), a significant reduction was observed only in MYXV vs. MYXV+NK (3.66±0.58 vs. 0.66±0.07 fold increase, difference = 3.00±0.58, 95% CI = 1.663 to 4.344, P3 = .0009). Error bars represent 95% confidence intervals. (C) Survival curves showing that mice treated with MYXV+NK survived significantly longer than PBS (median survival for PBS-treated group vs. MYXV+NK was 51.5 days vs. 100%, hazard ratio (HR) = 30.89, 95% CI of HR = 3.333 to 286.2, log-rank P1 = .0025) or NK-treated mice (median survival for NK-treated group vs. MYXV+NK was 67 days vs. 100%, HR = 20.60, 95% CI of HR = 3.007 to 141.1, log-rank P2 = .0021) but not with MYXV-treated mice (median survival for MYXV vs. MYXV+NK-treated group was 60% vs. 100%, HR = 8.366, 95% CI of HR = 0.5188 to 134.9, log-rank P2 = .1343). Experiment was terminated on day 159 post tumor implantation.