Fig. 7: αPD-1 shows active efficacy in Saa1-/- and Stat3 flox/floxAlb-cre+ (lacked Stat3 in hepatocytes) orthotopic HCC mouse models. | Nature Communications

Fig. 7: αPD-1 shows active efficacy in Saa1-/- and Stat3flox/floxAlb-cre+ (lacked Stat3 in hepatocytes) orthotopic HCC mouse models.

From: Serum amyloid A promotes glycolysis of neutrophils during PD-1 blockade resistance in hepatocellular carcinoma

Fig. 7: αPD-1 shows active efficacy in Saa1-/- and Stat3 flox/floxAlb-cre+ (lacked Stat3 in hepatocytes) orthotopic HCC mouse models.

a Hepa1-6-luci+ cells were orthotopic implanted in the liver of Saa1+/+, Saa1-/- mice, Stat3flox/floxAlb-cre+, and Stat3flox/floxAlb-cre- mice, separately. n = 4 mice. Mice were treated with αPD-1 (10 mg/kg) for three days. Meanwhile, D-luciferin (100 mg/kg) was injected intraperitoneally for detecting bioluminescence in vivo by IVIS every four days. After 18 days, the mice were sacrificed. The whole body and liver of mice were weighed. The dissected tumor was prepared for histological examination and immunofluorescence analysis. b Luciferase was detected on day 7 (1st αPD-1), 11 (2nd αPD-1), and 15 (3rd αPD-1) of Saa1+/+ and Saa1–/– mice. n = 4 mice. c Images of tumor were taken from Saa1+/+ and Saa1–/– mice. Histograms showed weight changes in the whole mice, liver tumor, and liver to mouse ratio in different groups. n = 4 mice. The confocal microscopy images showed the co-expression of SAA, PD-L1, MPO+ neutrophils (d), IFNγ+CD8+ T cells and MPO+ neutrophils (e) and quantification of MPO+ cells, PD-L1+MPO+ cells and IFNγ+CD8+ T cells in peritumor (f) in Saa1+/+ and Saa1-/- mice by immunofluorescence analysis. n = 4 mice. g Luciferase was detected on day 15 (3rd αPD-1) of Stat3flox/floxAlb-cre+ and Stat3flox/floxAlb-cre- mice. h Images of tumor tissue were taken from Stat3flox/floxAlb-cre+ and Stat3flox/floxAlb-cre- mice. Histograms showed weight changes in the whole mouse, liver tumor, and liver to mouse ratio in different groups. n = 4 mice. The confocal microscopy images showed the co-expression of SAA, PD-L1, MPO+ neutrophils (i), IFNγ+CD8+ T cells and MPO+ neutrophils ( j) and quantification of MPO+ cells, PD-L1+MPO+ cells and IFNγ+CD8+ T cells in peritumor (k) in Stat3flox/floxAlb-cre+ and Stat3flox/floxAlb-cre- mice by immunofluorescence analysis. n = 4 mice. CD8: dark red, DAPI: blue, IFNγ: yellow, MPO: green, PD-L1: orange, and SAA: brilliant red. The results are expressed as the mean ± SEM. Statistical data presented in this figure show mean ± SEM. ns indicates P > 0.05, *P < 0.05, **P < 0.01, and ***P < 0.001, by two-sided Student’s t test (c, f, h, k). Source data and exact P values are provided as a Source Data file. Illustrations created with BioRender.com.

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