Fig. 5
A high level of IL-15 expression in lung adenocarcinoma is related to a favorable prognosis. (A), Expression of IL-15 in lung adenocarcinoma cells at different stages (n = 12 samples per stage). Scale bar, 100 μm. ****, p < 0.0001. (B), Kaplan-Meier plotter analysis of survival probability according to the expression level of IL-15 (high expression, n = 278; low expression, n = 226, p = 0.0202). (C), LLC cells transduced with Lv-mIL-15 or Lv-mCtrl were inoculated subcutaneously into C57BL/6 mice (1 × 106 cells/mouse, n = 7 mice/group). Tumor volumes were calculated, and the data are presented as the means ± SDs. Two-way ANOVA followed by Sidak’s multiple comparison test was used. ****, p < 0.0001. (D), The concentration of IL-15 in the tumor interstitial fluid was measured via ELISA. Each point in the graph represents an individual mouse. The data are presented as the means ± SDs. *, p < 0.05. (E), Representative images of tumor-infiltrating CD8+ T cells. Scale bar, 50 μm. **, p < 0.01. (F), TILs were enriched in the tumors and stained with antibodies against CD45, CD3, CD8, Ki67, and perforin. The data are presented as the means ± SDs (n = 5). *, p < 0.05; **, p < 0.01. (G), LLC cells transduced with Lv-mIL-15 (n = 5) or Lv-mCtrl (n = 3) were injected intravenously into C57BL/6 mice. The mice were treated with an isotype control or an anti-PD-L1 antibody (10 mg/kg). The mice were euthanized on day 9 after the initial anti-PD-L1 treatment. Lung tissues were subjected to H&E staining. Scale bar, 50 μm. **, p < 0.01; ****, p < 0.0001. (H), Representative images of tumor-infiltrating CD8+ T cells in the lungs of C57BL/6 mice. Scale bar, 50 μm. ***, p < 0.001. (I), Twelve freshly collected human lung tumor explants were treated with the anti-PD-1 mAb (10 µg/ml) for 24 h. TILs were isolated from these explants and stained with antibodies against granzyme B. Five explants responded to anti-PD-1 treatment, while seven explants did not respond to anti-PD-1 treatment. **, p < 0.01. (J), The levels of IL-15 expression in human lung tumor samples were evaluated using the average integrated optical density (average IOD). ***, p < 0.001