Figure 3. IFNγ sculpts metabolic state in tumors during immunoediting.

(A) Illustration of experimental design of IFNγ neutralization.

(B and C) Tumor growth (B) and tumor weight (C) of Braf/Pten melanomas from indicated groups. (D and E) Representative histology images (D) and quantitative results (E) for staining of Ki67, senescence-associated β-galactosidase activity (SA-β-gal), apoptotic cells with TUNEL, p21, and PD-L1 (labeled with Alexa Fluor-488 conjugated secondary antibody) in indicated groups. Slides were counterstained with hematoxylin in chromogenic sections, counterstained with nuclear fast red in β-gal assay, and counterstained with DAPI in immunofluorescence staining. Scale bars, 50 μm.

(F–H) Tumor growth curve for KO1 (F), KO3 (G), and KO7 (H), three Braf/Pten melanoma cell lines derived from adaptive immune-cell-deficient Braf/Pten mouse, after subcutaneously engrafting into C57BL/6 wild-type mice and IFNγ^−/− mice (n = 6–8 per group).

(I) Tumor growth of Braf/Pten melanomas from PBS treatment (Control) and anti-IFNγ mAb treatment group.

(J) Metabolite set enrichment analysis of Braf/Pten tumors from anti-IFNγ antibody treatment group versus matched control group.

Data are the cumulative results from at least two independent experiments (B and C) or are representative images of two independent experiments with similar results (E–I). Each symbol represents one individual (C) or represents the average of positive percentage from random 4 field in a section of individual tumor (E). Data are means ± SEM and analyzed by two-tailed, unpaired Student’s t test.