Figure 3. Combined disruption of IL-6 and CXCL8 signaling reduces or eliminates metastatic lung colonization.

Mice inoculated with 1 × 10⁶ luciferase-expressing OS-17 cells were treated with pharmacologic inhibitors of IL-6 (sc144, inhibitor of IL-6ST), CXCL8 (DF2156A, inhibitor of CXCR1 and -2), or both. (A) Bioluminescent imaging completed at 28 days after inoculation. (B) Gross appearance of representative lung blocks taken from the mice identified with red frames in A at the time of euthanasia (endpoint criteria, or day 200 for mice 1 and 9 of combined treatment group) shows no microscopic evidence of tumor in long-term survivors. This included some mice, such as mouse 10 of the combined treatment group (endpoint at day 72) that showed response at early time points, but subsequently developed metastasis. Scale bar: 2 mm. (C) Quantification of the lung-field bioluminescence from day 14 (n = 10 mice per group). (D) Survival analysis of the mice shown in A. As noted, treatment continued until day 42, then was stopped. Mice that received combination therapy experienced significantly better outcomes than those who received no treatment or treatment with only 1 inhibitor (n = 10 mice per group, P value in comparison to vehicle control). (E) Validation studies confirm the results found in A. Mice surviving beyond 200 days were euthanized. Mice that died during the study, but had no evidence of metastatic tumor burden on necropsy (n = 3) were censored in this analysis (n = 25 mice per group). No Tx, no treatment. **P < 0.01; ****P < 0.0001 by 1-way ANOVA with Tukey’s post hoc test (C) or Mantel-Cox log-rank test (D and E).