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Metabolic alterations in SPP1 + KYNU + macrophages remodel the immunosuppressive microenvironment in MPNST. (A) Representative image of mIHC results displaying the expression differences of SPP1 + KYNU + /SPP1 + <t>IDO1</t> + macrophages (SPP1 + KYNU + CD163 + /SPP1 + IDO1 + CD163 + ) in PNF and MPNST tissues, captured at 40× (scale bars: 100 µm) and 120× magnification (scale bars: 50 µm), with quantification of SPP1 + KYNU + and SPP1 + IDO1 + cells per HP ( n = 3); (B) Live‐cell microscopy of Schwann cell (ipNF05.5) dynamics co‐cultured with macrophages over 48 h, with quantitative analysis of migration speed using Livecyte kinetic cytometer. (C) Alterations in cytokine secretion levels by macrophages under NC‐OE, SPP1‐OE, and SPP1‐OE with IDO1 inhibitor treatment, with quantitative analysis ( n = 3). (D) Chord diagram showing key receptor–ligand interactions between different SPP1 + macrophage subpopulations and T cells. (E) Dot plot showing the differences in T cell expression of regulatory T cell (Treg) and exhausted T cell (Tex) markers between PNF and MPNST. (F) Representative image of mIHC results displaying the expression differences of PD‐1 + T cells (PD‐1 + CD8A + ) between benign and malignant neurofibromas, along with the spatial distribution of macrophages (CD68 + ). Quantitative data are presented as mean ± SD, with significance levels indicated as (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001).
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Metabolic alterations in SPP1 + KYNU + macrophages remodel the immunosuppressive microenvironment in MPNST. (A) Representative image of mIHC results displaying the expression differences of SPP1 + KYNU + /SPP1 + <t>IDO1</t> + macrophages (SPP1 + KYNU + CD163 + /SPP1 + IDO1 + CD163 + ) in PNF and MPNST tissues, captured at 40× (scale bars: 100 µm) and 120× magnification (scale bars: 50 µm), with quantification of SPP1 + KYNU + and SPP1 + IDO1 + cells per HP ( n = 3); (B) Live‐cell microscopy of Schwann cell (ipNF05.5) dynamics co‐cultured with macrophages over 48 h, with quantitative analysis of migration speed using Livecyte kinetic cytometer. (C) Alterations in cytokine secretion levels by macrophages under NC‐OE, SPP1‐OE, and SPP1‐OE with IDO1 inhibitor treatment, with quantitative analysis ( n = 3). (D) Chord diagram showing key receptor–ligand interactions between different SPP1 + macrophage subpopulations and T cells. (E) Dot plot showing the differences in T cell expression of regulatory T cell (Treg) and exhausted T cell (Tex) markers between PNF and MPNST. (F) Representative image of mIHC results displaying the expression differences of PD‐1 + T cells (PD‐1 + CD8A + ) between benign and malignant neurofibromas, along with the spatial distribution of macrophages (CD68 + ). Quantitative data are presented as mean ± SD, with significance levels indicated as (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001).
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Metabolic alterations in SPP1 + KYNU + macrophages remodel the immunosuppressive microenvironment in MPNST. (A) Representative image of mIHC results displaying the expression differences of SPP1 + KYNU + /SPP1 + <t>IDO1</t> + macrophages (SPP1 + KYNU + CD163 + /SPP1 + IDO1 + CD163 + ) in PNF and MPNST tissues, captured at 40× (scale bars: 100 µm) and 120× magnification (scale bars: 50 µm), with quantification of SPP1 + KYNU + and SPP1 + IDO1 + cells per HP ( n = 3); (B) Live‐cell microscopy of Schwann cell (ipNF05.5) dynamics co‐cultured with macrophages over 48 h, with quantitative analysis of migration speed using Livecyte kinetic cytometer. (C) Alterations in cytokine secretion levels by macrophages under NC‐OE, SPP1‐OE, and SPP1‐OE with IDO1 inhibitor treatment, with quantitative analysis ( n = 3). (D) Chord diagram showing key receptor–ligand interactions between different SPP1 + macrophage subpopulations and T cells. (E) Dot plot showing the differences in T cell expression of regulatory T cell (Treg) and exhausted T cell (Tex) markers between PNF and MPNST. (F) Representative image of mIHC results displaying the expression differences of PD‐1 + T cells (PD‐1 + CD8A + ) between benign and malignant neurofibromas, along with the spatial distribution of macrophages (CD68 + ). Quantitative data are presented as mean ± SD, with significance levels indicated as (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001).
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Metabolic alterations in SPP1 + KYNU + macrophages remodel the immunosuppressive microenvironment in MPNST. (A) Representative image of mIHC results displaying the expression differences of SPP1 + KYNU + /SPP1 + <t>IDO1</t> + macrophages (SPP1 + KYNU + CD163 + /SPP1 + IDO1 + CD163 + ) in PNF and MPNST tissues, captured at 40× (scale bars: 100 µm) and 120× magnification (scale bars: 50 µm), with quantification of SPP1 + KYNU + and SPP1 + IDO1 + cells per HP ( n = 3); (B) Live‐cell microscopy of Schwann cell (ipNF05.5) dynamics co‐cultured with macrophages over 48 h, with quantitative analysis of migration speed using Livecyte kinetic cytometer. (C) Alterations in cytokine secretion levels by macrophages under NC‐OE, SPP1‐OE, and SPP1‐OE with IDO1 inhibitor treatment, with quantitative analysis ( n = 3). (D) Chord diagram showing key receptor–ligand interactions between different SPP1 + macrophage subpopulations and T cells. (E) Dot plot showing the differences in T cell expression of regulatory T cell (Treg) and exhausted T cell (Tex) markers between PNF and MPNST. (F) Representative image of mIHC results displaying the expression differences of PD‐1 + T cells (PD‐1 + CD8A + ) between benign and malignant neurofibromas, along with the spatial distribution of macrophages (CD68 + ). Quantitative data are presented as mean ± SD, with significance levels indicated as (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001).
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Metabolic alterations in SPP1 + KYNU + macrophages remodel the immunosuppressive microenvironment in MPNST. (A) Representative image of mIHC results displaying the expression differences of SPP1 + KYNU + /SPP1 + <t>IDO1</t> + macrophages (SPP1 + KYNU + CD163 + /SPP1 + IDO1 + CD163 + ) in PNF and MPNST tissues, captured at 40× (scale bars: 100 µm) and 120× magnification (scale bars: 50 µm), with quantification of SPP1 + KYNU + and SPP1 + IDO1 + cells per HP ( n = 3); (B) Live‐cell microscopy of Schwann cell (ipNF05.5) dynamics co‐cultured with macrophages over 48 h, with quantitative analysis of migration speed using Livecyte kinetic cytometer. (C) Alterations in cytokine secretion levels by macrophages under NC‐OE, SPP1‐OE, and SPP1‐OE with IDO1 inhibitor treatment, with quantitative analysis ( n = 3). (D) Chord diagram showing key receptor–ligand interactions between different SPP1 + macrophage subpopulations and T cells. (E) Dot plot showing the differences in T cell expression of regulatory T cell (Treg) and exhausted T cell (Tex) markers between PNF and MPNST. (F) Representative image of mIHC results displaying the expression differences of PD‐1 + T cells (PD‐1 + CD8A + ) between benign and malignant neurofibromas, along with the spatial distribution of macrophages (CD68 + ). Quantitative data are presented as mean ± SD, with significance levels indicated as (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001).
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Metabolic alterations in SPP1 + KYNU + macrophages remodel the immunosuppressive microenvironment in MPNST. (A) Representative image of mIHC results displaying the expression differences of SPP1 + KYNU + /SPP1 + <t>IDO1</t> + macrophages (SPP1 + KYNU + CD163 + /SPP1 + IDO1 + CD163 + ) in PNF and MPNST tissues, captured at 40× (scale bars: 100 µm) and 120× magnification (scale bars: 50 µm), with quantification of SPP1 + KYNU + and SPP1 + IDO1 + cells per HP ( n = 3); (B) Live‐cell microscopy of Schwann cell (ipNF05.5) dynamics co‐cultured with macrophages over 48 h, with quantitative analysis of migration speed using Livecyte kinetic cytometer. (C) Alterations in cytokine secretion levels by macrophages under NC‐OE, SPP1‐OE, and SPP1‐OE with IDO1 inhibitor treatment, with quantitative analysis ( n = 3). (D) Chord diagram showing key receptor–ligand interactions between different SPP1 + macrophage subpopulations and T cells. (E) Dot plot showing the differences in T cell expression of regulatory T cell (Treg) and exhausted T cell (Tex) markers between PNF and MPNST. (F) Representative image of mIHC results displaying the expression differences of PD‐1 + T cells (PD‐1 + CD8A + ) between benign and malignant neurofibromas, along with the spatial distribution of macrophages (CD68 + ). Quantitative data are presented as mean ± SD, with significance levels indicated as (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001).
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Metabolic alterations in SPP1 + KYNU + macrophages remodel the immunosuppressive microenvironment in MPNST. (A) Representative image of mIHC results displaying the expression differences of SPP1 + KYNU + /SPP1 + <t>IDO1</t> + macrophages (SPP1 + KYNU + CD163 + /SPP1 + IDO1 + CD163 + ) in PNF and MPNST tissues, captured at 40× (scale bars: 100 µm) and 120× magnification (scale bars: 50 µm), with quantification of SPP1 + KYNU + and SPP1 + IDO1 + cells per HP ( n = 3); (B) Live‐cell microscopy of Schwann cell (ipNF05.5) dynamics co‐cultured with macrophages over 48 h, with quantitative analysis of migration speed using Livecyte kinetic cytometer. (C) Alterations in cytokine secretion levels by macrophages under NC‐OE, SPP1‐OE, and SPP1‐OE with IDO1 inhibitor treatment, with quantitative analysis ( n = 3). (D) Chord diagram showing key receptor–ligand interactions between different SPP1 + macrophage subpopulations and T cells. (E) Dot plot showing the differences in T cell expression of regulatory T cell (Treg) and exhausted T cell (Tex) markers between PNF and MPNST. (F) Representative image of mIHC results displaying the expression differences of PD‐1 + T cells (PD‐1 + CD8A + ) between benign and malignant neurofibromas, along with the spatial distribution of macrophages (CD68 + ). Quantitative data are presented as mean ± SD, with significance levels indicated as (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001).
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Metabolic alterations in SPP1 + KYNU + macrophages remodel the immunosuppressive microenvironment in MPNST. (A) Representative image of mIHC results displaying the expression differences of SPP1 + KYNU + /SPP1 + IDO1 + macrophages (SPP1 + KYNU + CD163 + /SPP1 + IDO1 + CD163 + ) in PNF and MPNST tissues, captured at 40× (scale bars: 100 µm) and 120× magnification (scale bars: 50 µm), with quantification of SPP1 + KYNU + and SPP1 + IDO1 + cells per HP ( n = 3); (B) Live‐cell microscopy of Schwann cell (ipNF05.5) dynamics co‐cultured with macrophages over 48 h, with quantitative analysis of migration speed using Livecyte kinetic cytometer. (C) Alterations in cytokine secretion levels by macrophages under NC‐OE, SPP1‐OE, and SPP1‐OE with IDO1 inhibitor treatment, with quantitative analysis ( n = 3). (D) Chord diagram showing key receptor–ligand interactions between different SPP1 + macrophage subpopulations and T cells. (E) Dot plot showing the differences in T cell expression of regulatory T cell (Treg) and exhausted T cell (Tex) markers between PNF and MPNST. (F) Representative image of mIHC results displaying the expression differences of PD‐1 + T cells (PD‐1 + CD8A + ) between benign and malignant neurofibromas, along with the spatial distribution of macrophages (CD68 + ). Quantitative data are presented as mean ± SD, with significance levels indicated as (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001).

Journal: MedComm

Article Title: Metabolic Alterations in Macrophage Subtypes Propel Immune and Stromal Remodeling in Neurofibroma's Malignant Progression

doi: 10.1002/mco2.70709

Figure Lengend Snippet: Metabolic alterations in SPP1 + KYNU + macrophages remodel the immunosuppressive microenvironment in MPNST. (A) Representative image of mIHC results displaying the expression differences of SPP1 + KYNU + /SPP1 + IDO1 + macrophages (SPP1 + KYNU + CD163 + /SPP1 + IDO1 + CD163 + ) in PNF and MPNST tissues, captured at 40× (scale bars: 100 µm) and 120× magnification (scale bars: 50 µm), with quantification of SPP1 + KYNU + and SPP1 + IDO1 + cells per HP ( n = 3); (B) Live‐cell microscopy of Schwann cell (ipNF05.5) dynamics co‐cultured with macrophages over 48 h, with quantitative analysis of migration speed using Livecyte kinetic cytometer. (C) Alterations in cytokine secretion levels by macrophages under NC‐OE, SPP1‐OE, and SPP1‐OE with IDO1 inhibitor treatment, with quantitative analysis ( n = 3). (D) Chord diagram showing key receptor–ligand interactions between different SPP1 + macrophage subpopulations and T cells. (E) Dot plot showing the differences in T cell expression of regulatory T cell (Treg) and exhausted T cell (Tex) markers between PNF and MPNST. (F) Representative image of mIHC results displaying the expression differences of PD‐1 + T cells (PD‐1 + CD8A + ) between benign and malignant neurofibromas, along with the spatial distribution of macrophages (CD68 + ). Quantitative data are presented as mean ± SD, with significance levels indicated as (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001).

Article Snippet: Linrodostat (BMS‐986205, ONO‐7701), acquired from MedChemExpress, was used as the IDO1 inhibitor at a concentration of 1 μM in our study.

Techniques: Expressing, Microscopy, Cell Culture, Migration, Cytometry