Fig. 4: HEI3090-induced IL-18 production is required to inhibit tumor growth. | Nature Communications

Fig. 4: HEI3090-induced IL-18 production is required to inhibit tumor growth.

From: A small-molecule P2RX7 activator promotes anti-tumor immune responses and sensitizes lung tumor to immunotherapy

Fig. 4

a Average tumor area of LLC allograft in WT mice injected with IL-1β and IL-18 neutralizing antibodies and daily treatment with HEI3090. Curves showed mean tumor area in mm2 ± SEM (vehicle n = 28, HEI3090 n = 32, HEI3090 + IL-1β treated n = 6, HEI3090 + IL-18 n = 8. Two-way Anova test). b Average tumor area and tumor weight of LLC allograft in il-18-deficient mice (il-18−/−) and daily treatment with HEI3090. Curves showed mean tumor area in mm2 ± SEM (vehicle n = 9, HEI3090 n = 10. Two-way Anova test, left panel) and graph showed tumor weight the day of sacrifice. Data are presented by violin plots showing all points with hatched bar corresponding to median tumor weight (vehicle n = 9, HEI3090 n = 10. Two-tailed Mann–Whitney test, right panel). c Representative images of IL-18 staining in LLC tumors of six mice studied. Bar = 50 µm. d Production of IL-18 and IL-1β in serum of treated mice determined by ELISA. Data are presented by violin plots showing all points with plain bar corresponding to median cytokine concentration (IL-18 production: vehicle n = 7, HEI3090 n = 8, HEI3090 + αIL-18 n = 6, vehicle p2rx7−/− n = 5, HEI3090 p2rx7−/− n = 8, (IL-1β production: vehicle n = 13, HEI3090 n = 12, HEI3090 + αIL-18 n = 10, vehicle p2rx7−/− n = 10, HEI3090 p2rx7−/− n = 12. Two-tailed Mann–Whitney test). e Ex vivo production of IL-18 in primary peritoneal macrophages. Data are presented by violin plots showing all points with hatched bar corresponding to median cytokine concentration (no treatment n = 4, HEI3090 n = 4, ATP 1 mM n = 4, ATP 1 mM + HEI3090 n = 4, ATP 3 mM n = 13, ATP 3 mM + HEI3090 n = 13, ATP 3 mM + MCC950 n = 3, ATP 3 mM + HEI3090 + MCC950 n = 3. Two-tailed Mann–Whitney test). f Representative images of IL-18 staining in lung tumor lesions from LSL-KrasG12D mice over four mice studied (bar = 100 µm) and production of IL-18 in serum of LSL-KrasG12D mice. Data are presented by violin plots showing all points with hatched bar corresponding to median IL-18 concentration (vehicle + αPD-1, n = 4, HEI3090 + αPD-1, n = 6. Two-tailed Mann–Whitney test). p values: *p < 0.05, **p < 0.01, ****p < 0.0001. Source data are provided as a Source Data file.

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