Fig. 7

Immunomodulatory function of shTRAIL and combination therapy in humanized mice. A Correlation analysis of CCL2 with TRAIL or TRAIL-R in breast and colorectal cancer based on the TCGA database (TNFRSF10A, TNFRSF10B, TNFRSF10C, and TNFRSF10D were TRAIL-R; TNFSF10 was TRAIL). B After MCF7, HCT116, and SW620 cells were incubated with shTRAIL for 24 h, the levels of Ccl2 mRNA were analyzed by real-time RT-PCR and normalized to GAPDH (n = 3). C Experimental layout. huHSC-NPG.GM3 mice were subcutaneously (s.c.) inoculated with 1 × 10⁶ HCT116 cells in the right flanks, and shTRAIL was injected intraperitoneally(i.p.) for eight consecutive days. At 21 d, the immune cells were assayed by flow cytometry (n = 5). D Tumor growth curves and tumor weights. E The percentages of intratumoral CD4⁺ T cells (CD45⁺CD4⁺), CD8⁺ T cells (CD45⁺CD8⁺), Tregs (CD45⁺CD4⁺CD25⁺Foxp3⁺), M2-TAMs (CD14⁺CD163⁺CD206⁺), and IL-10⁺ M2 (n = 5). F Tumor growth in humanized mice. Mice bearing HCT116 tumors were treated with PBS, shTRAIL (2 mg/kg), trabectedin (0.15 mg/kg/per mouse), or a combination of shTRAIL and trabectedin. Trabectedin was administered intravenously (i.v.) once a week. G The percentages of intratumoral lymphocytes (CD45⁺), activated CD8⁺ T cells (CD45⁺CD8⁺CD69⁺), Tregs (CD45⁺CD4⁺CD25⁺Foxp3⁺), M1-TAMs (CD14⁺CD86⁺CD80⁺), and IL-10⁺ M2(CD14⁺CD163⁺CD206⁺IL-10⁺) (n = 5). A two-way ANOVA test was used to compare the tumor growth responses. One-way ANOVA was performed to calculate the significant differences between groups, followed by LSD analysis. *P < 0.05; **P < 0.01; ***P < 0.001; and ****P < 0.0001