Figure 1.

hetIL-15 delays tumor growth and promotes tumor-infiltrating lymphocytes proliferation and survival. Mice, implanted with 2×10⁵ MC38 cells at day −5, were randomized in two different treatment groups: hetIL-15 (blue traingle) and PBS (gray square) administration. hetIL-15 (3 µg/injection/mouse) was injected IP three times per week. (A) Control mice (n=10) and hetIL-15-treated mice (n=9) received eight injections, starting at day 0, and tumor growth was monitored overtime. Tumor size measurements were performed every 2 to 3 days. Tumor area (length×width) mean±SEM for each time point are shown. Similar results were obtained in three independent experiments. (B–G) MC38 tumor-bearing mice were sacrificed at day eight after treatment with either PBS or hetIL-15 (1 day after the fourth administration). Tumor immune infiltrates were analyzed by flow cytometry to determine: (B) frequency of tumor-infiltrating CD8⁺ T cells. Data of three independent experiments were combined; (C) percentage of dividing tumor infiltrating CD8⁺T cells; (D) expression of the survival factor Bcl-2 in the tumor-infiltrating CD8⁺ T cell population; (E) frequency of tumor-infiltrating NK cells; (F) percentage of dividing tumor infiltrating NK cells; (G) intratumoral CD8⁺ T cells/Treg ratio for each treatment group. Bars represent mean±SEM. P values are from Mann-Whitney U test. hetIL-15, heterodimeric interleukin-15; IP, intraperitoneal; MFI, mean fluorescence intensity; NK, natural killer; SEM, Standard error of the mean.