Fig. 5: iDAMP blockade inhibits tumor growth by promoting pro-inflammatory DC maturation. | Nature Communications

Fig. 5: iDAMP blockade inhibits tumor growth by promoting pro-inflammatory DC maturation.

From: Cell death-induced immunogenicity enhances chemoimmunotherapeutic response by converting immune-excluded into T-cell inflamed bladder tumors

Fig. 5

a Percent growth curves (top) and tumor weight (bottom) of G69 tumors from vehicle (n = 7 biologically independent animals), Celecoxib (n = 7 biologically independent animals), GC (n = 8 biologically independent animals), and GC+ Celecoxib-treated mice (n = 7 biologically independent animals) upon two cycles of chemotherapy. Percent tumor growth was obtained by normalizing to starting tumor volumes. Doted gray rectangles denote the starting point and the end point of each GC cycle. Celecoxib was injected ip 48 h before GC treatment initiation and continued daily to endpoint. Data are presented as mean values ± SEM. (Top: One-way ANOVA-Tukey’s multiple comparisons test. GC+ Celex vs Vehicle p = 0.006; vs Celex p = 0.029; vs GC p = 0.001; Bottom: One-way ANOVA-Tukey’s multiple comparisons test. GC+ Celex vs Vehicle p = 0.0006; vs Celex p = 0.007; vs GC p = 0.019). b Percent growth curves (top) and tumor weight (bottom) of G7 tumors from vehicle (n = 5 biologically independent animals), Celecoxib (n = 6 biologically independent animals), GC (n = 8 biologically independent animals), and GC+ celecoxib-treated mice (n = 8 biologically independent animals) upon two cycles of chemotherapy. Data are presented as mean values ± SEM. (One-way ANOVA-Tukey’s multiple comparisons test. GC+ Celex vs Vehicle; vs Celex p = 0.0002; vs Celex p = 0.0003; vs GC p = 0.028; Bottom: One-way ANOVA-Tukey’s multiple comparisons test. GC+ Celex vs Vehicle p < 0.0001; vs Celex p = 0.002; vs GC p = 0.004). c, d Flow cytometry plots and corresponding quantification of CD11c + MHCII + dendritic cells (DC) from vehicle (n = 11 biologically independent samples), Celecoxib (n = 5 biologically independent samples), GC (n = 12 biologically independent samples), and GC+ Celecoxib-treated (n = 12 biologically independent samples) G69-tumor tissues. Data are presented as mean values ± SEM. e Relative quantification (%CD11c + MHC2+) of H2-K, CD86, and CD40 expression in tumor-infiltrating DCs from vehicle (n = 6 biologically independent samples), celecoxib (n = 5 biologically independent samples), GC (n = 5 biologically independent samples), and GC+ Celecoxib-treated (n = 4 biologically independent samples) G69-tumor tissues. Data are presented as mean values ± SEM. (One-way ANOVA-Tukey’s multiple comparisons test. H2-k: Vehicle vs GC p < 0.0001, Celex vs GC p = <0.0001, GC vs GC+ Celex p = 0.004; CD86:Vehicle vs GC p = 0.047, Celex vs GC p = 0.038). f Mean fluorescence intensity (MFI) of IL12, IL10, and IL4 expression in CD11c + MHC2 + DCs from vehicle (n = 4 biologically independent samples), celecoxib (n = 5 biologically independent samples), GC (n = 6 biologically independent samples), and GC+ Celecoxib-treated (n = 5 biologically independent samples) G69-tumor tissues. Data are presented as mean values ± SEM. (One-way ANOVA-Tukey’s multiple comparisons test. IL10: Vehicle vs Celex p = 0.004, vs GC p = 0.006, Celex vs GC p = <0.0001, vs GC+ Celex p = 0.002, GC vs GC+ Celex p = 0.005; IL12:Vehicle vs Celex p = 0.02; vs GC p = 0.009). g Representative images of immunofluorescence analysis of CD8+ T cells (red) interaction with CD11c + DCs (green) and CRT + G69 cells (white) upon treatment with either GC or GC+ Celecoxib for 2 cycles (Scale bar: 100 μm; Images representative of n = 3 independent experiments). Source data are provided as a Source data file.

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