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. 2023 Jan 13;13:1014802. doi: 10.3389/fimmu.2022.1014802

Figure 1.

Figure 1

hetIL-15 improves doxorubicin efficacy in extending survival by inhibiting metastatic formation in the lungs and CTCs dissemination in the blood. (A) Cartoon showing the treatment design. 0.35-1x106 4T1 cells were orthotopically inoculated in Balb/c mice and the animals were randomized in four groups: (i) untreated (PBS), (ii) Dox (Doxorubicin)-treated, (iii) hetIL-15-treated and (iv) Dox+hetIL-15-treated. Treatment started on day 5 post tumor inoculation with Dox (5mg/kg IV, purple arrows) once per week, followed by hetIL-15 (3 μg/mouse IP, blue arrows) every other day until day 20. (B) Tumor growth curves for each group overtime until day 21. Data were merged from 6 independent studies (n=54-60). Tumor volume (mm3) ± SEM for each time point is shown. Statistical analysis was done by mixed effects analysis model and Tukey’s multiple comparisons test. (C) Percent survival of the mice in each group. Statistical analysis was performed by Log-rank (Mantel-Cox) test and data merged from two independent experiments (n=15-19). (D) Representative images from H&E-stained lung sections (left panel), and the percentage of tumor areas present in each mouse lungs (right panel, asterisks show the significance of difference from the untreated group) presented as mean ± SD for each group. Data derived from one survival study (n=5-8) of (C). Scale bar, 4mm. Statistical analysis was done by one-way ANOVA and Tukey’s multiple comparisons test. (E, F) Representative images (upper panels) from clonogenic assays showing SRB-stained tumor colonies derived from lungs (E) and blood (F), and tables with the number and the percentage (plotted in pies) of mice with different number of tumor colonies (lower panels) in each group on day 22. Data were merged from 3 independent experiments (n=16) for the lungs and 2 independent experiments (n=18-19) for the blood. Legend shows number of tumor colonies in 4 different ranges. *p < 0.05, **p < 0.01, ***p <0.001, ****p < 0.0001, SD, standard deviation; SEM, standard error of the mean. Image Credit: vector.me.