Fig. 7

Combination of CXCL14 neutralizing antibody with gemcitabine effectively hinders CALB2-mediated metastasis and improves survival outcome. (A) Liver metastases from the Calb2-OE tumor were isolated to establish liver metastasis (LM) organoids. After one week of splenic injection of LM organoids into the C57BL/6 mice, isotype IgG, αCXCL14 (1 mg/kg, intravenously), gemcitabine (25 mg/kg, intraperitoneally) or combined chemotherapy (αCXCL14 + gemcitabine) were injected twice per week for 4 consecutive weeks (top). Animal survival was monitored up to 60 days after injection (bottom). (B) Representative IVIS bioluminescence images, bright-field images, and H&E staining for metastatic lesions after 5 weeks of splenic injection of Calb2-OE-LM KPC organoids. Scale bars: 1 cm (left), 2000 μm (middle), 500 μm (right). (C-D) Quantification of living imaging, ex vivo liver imaging (C) and metastatic nodules (D) from B (n = 6 per group). (E) Kaplan-Meier survival curves for mice with KPC liver metastasis-derived organoid xenografts treated with the indicated regimen (n = 10 per group). (F) Schematic diagram illustrating the inflammatory reprogramming mechanism by which CALB2 promotes liver metastasis of PDAC. Error bars, mean ± SD; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; ns, not significant; by one-way ANOVA (C-D) or log-rank test (E)