Fig. 7: Combination therapy with VIP-R antagonist and anti-PD-1 promotes intra-tumoral T cell infiltration and decreases CXCR4 expression on T cells in tumor-draining lymph nodes. | Nature Communications

Fig. 7: Combination therapy with VIP-R antagonist and anti-PD-1 promotes intra-tumoral T cell infiltration and decreases CXCR4 expression on T cells in tumor-draining lymph nodes.

From: Targeting vasoactive intestinal peptide-mediated signaling enhances response to immune checkpoint therapy in pancreatic ductal adenocarcinoma

Fig. 7

KPC.Luc tumors were implanted subcutaneously in C57BL/6 mice. On day 15 after tumor implantation, GFP+ T cells were adoptively transferred (via tail vein injections) and mice were treated with ANT308 ± aPD-1 for 3 days. a A schematic showing GFP + T cell transfer and treatment strategy in mice with subcutaneous KPC.Luc tumors were created using BioRender. b Representative Hoescht-stained tumor tissues (blue for nucleus) for each treatment group. Zoom-in of two regions of interest (RO1) labeled as R0I-1 and ROI-2 in the original image of tumors of mice treated with ANT308 + aPD-1 is also shown. The experiment was performed once with all four groups imaged on the same day. Percentage of (c) CXCR4+ D69+ and (d) CXCR4 + Ki67+ cells in CD4+ (left) and CD8+ (right) subsets of T cells. e Tumor growth rate and (f) survival curves generated from mice with subcutaneous KPC.Luc tumors that were treated with scrambled peptide, IgG and PBS or ANT308 and aPD-1 or AMD3100 and aPD-1 or ANT308 and AMD3100 or a combination of ANT308, aPD-1, and AMD3100. Median tumor volume is represented as a dashed gray line. Statistical differences shown in panels (c, d) were determined via repeated measures ANOVA and Dunnett’s post-test with n = 4–5 mice per group. Statistical differences in f were determined via a Log-rank test (n = 9–10 mice per group). Straight lines in panels (c, d) show mean ± standard deviation. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

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