Journal: Molecular Medicine Reports

Article Title: Elevated IgG levels induce an M2-to-M1 phenotypic shift in mucosal macrophages and restrict the growth of invasive sphenoid sinus pituitary adenomas

doi: 10.3892/mmr.2026.13878

Figure Lengend Snippet: IFN-γ suppresses tumor growth and invasion. (A) Cytokine profiling of co-culture supernatants via ELISAs: IFN-γ, IL-1β, IL-6, IL-10, TGF-β and TNF-α. (B-D) Spatial expression patterns of IFN-γ. (B) Immunofluorescence imaging of the invasive front in SSIT, showing DAPI (blue), IBA-1 + macrophages (red) and IFN-γ + signals (green), and grayscale intensity distribution. (C) Immunofluorescence imaging of TIM and NIM, showing DAPI (blue), IBA-1 + macrophages (red) and IFN-γ + signals (green). (D) Quantification of relative IFN-γ expression in TIM and NIM. (E) Representative Ki-67 immunohistochemistry images of SSIT cases stratified into IFN-γ-high and IFN-γ-low groups (n=5 each; median split). (F) Quantification of Ki-67 index comparing the two groups. (G) EdU staining demonstrating dose-dependent suppression of TtT/GF pituitary adenoma cell proliferation by IFN-γ (0–100 ng/ml; 48 h). (H) Representative flow cytometry histograms for cell cycle analysis of cells treated with IFN-γ (0–100 ng/ml) in the absence (0 µM) or presence (5 µM) of ruxolitinib. (I) Stacked bar plot showing the percentages of cells in the G 1 , S and G 2 /M phases under the same treatment conditions. (A) One-way ANOVA with Tukey's post hoc multiple comparisons test. (D and F) Unpaired two-tailed Student's t-test. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. CTRL, control; DMC, digested mucosal culture; EdU, 5-ethynyl-2′-deoxyuridine; IBA-1, ionised calcium binding adaptor molecule 1; MTC, mucosal tissue culture; NIM, non-invaded mucosa; ns, not significant; PE-A, phycoerythrin-area; SSIT, sphenoid sinus-invasive tumor; TIM, tumor-invaded mucosa.

Article Snippet: TtT/GF cells (~1×10 6 ) were treated with the indicated concentrations of IFN-γ (0–100 ng/ml; cat. no. RP01038; ABclonal Biotech Co., Ltd.) or IL-6 (0–100 ng/ml; cat. no. RP00201; ABclonal Biotech Co., Ltd.) alone for 48 h at 37°C.

Techniques: Co-Culture Assay, Expressing, Immunofluorescence, Imaging, Immunohistochemistry, Staining, Flow Cytometry, Cell Cycle Assay, Two Tailed Test, Control, Binding Assay

Journal: Molecular Medicine Reports

Article Title: Elevated IgG levels induce an M2-to-M1 phenotypic shift in mucosal macrophages and restrict the growth of invasive sphenoid sinus pituitary adenomas

doi: 10.3892/mmr.2026.13878

Figure Lengend Snippet: Elevated IgG levels drive macrophage M2-to-M1 reprogramming. (A) Sphenoid sinus-invasive tumor cases stratified into CD19-high (n=5) and CD19-low (n=5) groups based on the cohort median of CD19 + B cell density, with (B) quantitative analyses of macrophage polarization (M1-like versus M2-like). (C) Dural-invasive tumor and non-invasive tumor cases stratified into IgG-high (n=27) and IgG-low (n=26) groups based on the cohort median of relative IgG immunohistochemistry staining intensity, with (D) quantitative analyses of M1-like/M2-like macrophage proportions. (E and F) RAW264.7 macrophages were pre-polarized with IL-4 (20 ng/ml) or with lipopolysaccharide (100 ng/ml) plus IFN-γ (20 ng/ml) for 24 h, followed by IgG (10 µg/ml) exposure. Relative (E) IL-6 and (F) TNF-α mRNA expression in RAW264.7 macrophages pre-polarized to M0, M1 or M2 states. (G) Representative flow cytometric cell-cycle profiles of TtT/GF cells following the indicated treatments. (H) Stacked bar plot summarizing the percentages of cells from (G) in G 1 , S and G 2 /M phases. (I) Representative images from the scratch wound assay at 0, 24, 48 and 72 h under the indicated treatments. (J) Quantification of scratch wound closure. (K) Representative western blot images showing total STAT1, p-STAT1, total STAT3, p-STAT3 and β-actin levels in cells treated with IFN-γ (100 ng/ml), IL-6 (100 ng/ml), IFN-γ + IL-6 (50 ng/ml each), ruxolitinib (5 µM) or IFN-γ + IL-6 (50 ng/ml each) plus ruxolitinib (5 µM), as indicated. (L) Densitometric semi-quantification of p-STAT1/STAT1 (ratio). (B and D) Unpaired two-tailed Student's t-test. (E, F, J and L) One-way ANOVA with Tukey's post hoc multiple comparisons test. *P<0.05, ***P<0.001, ****P<0.0001. CTRL, control; IBA-1, ionised calcium binding adaptor molecule 1; ns, not significant; p-, phosphorylated; PE-A, phycoerythrin-area.

Article Snippet: TtT/GF cells (~1×10 6 ) were treated with the indicated concentrations of IFN-γ (0–100 ng/ml; cat. no. RP01038; ABclonal Biotech Co., Ltd.) or IL-6 (0–100 ng/ml; cat. no. RP00201; ABclonal Biotech Co., Ltd.) alone for 48 h at 37°C.

Techniques: Immunohistochemistry, Staining, Expressing, Scratch Wound Assay Assay, Western Blot, Two Tailed Test, Control, Binding Assay

Journal: Molecular Medicine Reports

Article Title: Elevated IgG levels induce an M2-to-M1 phenotypic shift in mucosal macrophages and restrict the growth of invasive sphenoid sinus pituitary adenomas

doi: 10.3892/mmr.2026.13878

Figure Lengend Snippet: Summary graphic illustration. This illustration summarizes the proposed model during pituitary adenoma invasion. The tumor invasive front abuts an intact sphenoid sinus mucosa, forming a distinct boundary. The mucosal compartment is enriched for ionised calcium binding adaptor molecule 1-positive macrophages with an M1-like predominance and IgG-high B cells. B cell-derived IgG promotes M2-to-M1 macrophage reprogramming, while coordinated IFN-γ and IL-6 production establishes a tumor-suppressive cytokine gradient that decreases from mucosa toward the tumor core, constraining proliferation and migration via JAK-STAT1 activation. Therapeutically, anti-CD47 monoclonal antibody blocks the CD47-SIRPα ‘don't-eat-me’ axis and augments antibody-dependent cellular phagocytosis, highlighting a strategy for immune checkpoint-targeted therapy that may complement surgical management. FcR, Fc receptor; JAK, Janus kinase; mAb, monoclonal antibody; p-, phosphorylated; SIRPα, signal regulatory protein-α.

Article Snippet: TtT/GF cells (~1×10 6 ) were treated with the indicated concentrations of IFN-γ (0–100 ng/ml; cat. no. RP01038; ABclonal Biotech Co., Ltd.) or IL-6 (0–100 ng/ml; cat. no. RP00201; ABclonal Biotech Co., Ltd.) alone for 48 h at 37°C.

Techniques: Binding Assay, Derivative Assay, Migration, Activation Assay