Journal: Nature Communications

Article Title: Paclitaxel drives TREM2 + macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

doi: 10.1038/s41467-026-69060-5

Figure Lengend Snippet: a Pooled efficacy comparisons of ORR in patients who received Nab-PTX versus PTX in breast cancer therapy. The blue boxes signify the effect size for each individual study, with their size reflective of the weight assigned to each study in the analysis. The whiskers extending from each blue box delineate the 95% confidence interval (CI) for the effect size of the respective study. The odds ratio (OR) was calculated using a random-effects model. Statistical significance was assessed by a two-sided test, with P < 0.05 considered statistically significant. b Pooled efficacy comparisons of the pCR in patients who received Nab-PTX versus PTX in breast cancer therapy. The blue boxes signify the effect size for each individual study, with their size reflective of the weight assigned to each study in the analysis. The whiskers extending from each blue box delineate the 95% confidence interval (CI) for the effect size of the respective study. The odds ratio (OR) was calculated using a random-effects model. Statistical significance was assessed by two-sided test, with P < 0.05 considered statistically significant. c Schematic of experimental design for patient samples. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p d UMAP plot and bar graph showing identified cell clusters of infiltrated macrophages of breast cancer patient tissues with indicated treatment and their proportion in the indicated groups. e Box plots showing the TREM2 expression levels in macrophage subsets across the indicated experimental groups. Two-sided Wilcoxon test. In the box plots, the center line corresponds to the median, box corresponds to the interquartile range (IQR), and whiskers 1.5 × IQR. f Violin-box plots showing the TREM2 expression levels in identified cell clusters of infiltrated macrophages using the scRNA-seq data. g Representative immunofluorescence staining of tissues from patients who received PTX treatments or not. h Representative immunofluorescence staining of tissues from patients who received Nab-PTX treatments or not. ns, not significant. Source data are provided as a Source Data file.

Article Snippet: The Nab-PTX (HY-P99974) was purchased from MedChemExpress and used at a concentration of 9 mg/kg.

Techniques: Expressing, Immunofluorescence, Staining

Journal: Nature Communications

Article Title: Paclitaxel drives TREM2 + macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

doi: 10.1038/s41467-026-69060-5

Figure Lengend Snippet: a Representative immunofluorescence staining of tissues from patients with and without lung metastases. b Quantification of TREM2-expressing macrophages in tissues from patients with and without lung metastases ( n = 5 patients per group). c Schematic of the experimental design in 4T1-Luc breast-tumor-bearing mice treated with DMSO or PTX. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p d Representative in vivo bioluminescence images of mice that received the indicated treatments ( n = 5 mice per group). e Representative bright-field images (left) and hematoxylin and eosin (H&E) staining (right) of lungs from mice injected orthotopically with 4T1-Luc cells and treated as described in ( c ) ( n = 5 mice per group). f Quantification (right) of the total numbers of lung-surface metastases ( n = 6 mice per group). g Representative flow cytometry analysis showing a histogram (left) and quantification (right) of the proportion of TREM2-expressing macrophages in tumors ( n = 3 mice per group). h Representative immunofluorescence staining of tumors in mice that received the indicated treatments. i Schematic of Nab-PTX treatment in Py8119 breast tumor-bearing mice. Mice were intraperitoneally injected with DMSO, PTX, PBS, or Nab-PTX at the indicated times. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p j Photographs (left) of tumors in mice that received the indicated treatments on day 14. Tumor weights (right) of mice that received the indicated treatments ( n = 6 mice per group). k Tumor volumes (right) of mice that received the indicated treatments ( n = 6 mice per group). l Representative bright-field images (left) of lungs from mice that received the indicated treatments. Quantification of the total numbers of lung-surface metastases is shown (right) ( n = 6 mice per group). m Representative H&E-stained images of lungs from mice that received the indicated treatments. n , o Representative flow cytometric analysis of pseudo-color plots ( n ) and quantification ( o ) showing the proportion of TREM2-expressing macrophages in tumors ( n = 4 mice per group). Data are shown as means ± S.D. and were analyzed by two-sided unpaired Student’s t test ( b , f and g ), two-sided one-way ANOVA followed by Tukey’s test ( j , l and o ) and two-sided two-way ANOVA followed by Tukey’s test ( k ). Source data are provided as a Source Data file.

Article Snippet: The Nab-PTX (HY-P99974) was purchased from MedChemExpress and used at a concentration of 9 mg/kg.

Techniques: Immunofluorescence, Staining, Expressing, In Vivo, Injection, Flow Cytometry

Journal: Nature Communications

Article Title: Paclitaxel drives TREM2 + macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

doi: 10.1038/s41467-026-69060-5

Figure Lengend Snippet: a Schematic of the experimental setup with THP1 or Raw264.7 cells with indicated treatment. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p b Quantification of proportion of TREM2 in THP1 and Raw264.7 cells with PTX. n = 3 biological independent samples. c Western blot of THP1 and Raw264.7 cells with indicated treatments. The experiment was independently repeated three times with similar results. d Schematic of the experimental strategy. CM was collected from tumor cells with the indicated treatment. TREM2 expression in macrophages incubated with the CM was assessed. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p e Quantification of proportion of TREM2 in THP1 incubated with CM of BT549 cells, SUM159 cells and MDA-MB-231 cells treated with PTX, in BMDM incubated with CM of Py8119 treated with PTX, in Raw264.7 incubated with CM from 4T1 and Py8119 cells treated with PTX, respectively. n = 3 biological independent samples. f Western blot analysis of TREM2 and related proteins in THP1, BMDMs, and Raw264.7 cells incubated with CM from BT549, SUM159, Py8119, and 4T1 cells, respectively. The experiment was independently repeated three times with similar results. g Representative immunofluorescence staining of THP1 cells incubated with BT549 CM. n = 3 biological independent samples. h Quantification of proportion of TREM2 in THP1 incubated with CM from BT549, SUM159, and MDA-MB-231 cells treated with Nab-PTX, respectively. n = 3 biological independent samples. i Quantification of the proportion of TREM2 in BMDM incubated with CM of Py8119 treated with Nab-PTX. n = 3 biological independent samples. j Cytokine array analysis of CM from BT549 cells treated indicated treatment. k Western blot analysis of the indicated proteins in Raw264.7 cells and BMDMs treated with recombinant FGF2. The experiment was independently repeated three times with similar results. l Quantification of the proportion of TREM2 in Raw264.7 cells and BMDMs treated with recombinant FGF2. n = 3 biological independent samples. m Schematic of the experimental strategy. CM was collected from tumor cells with the indicated treatment, and then pretreatment using an FGF2 neutralizing antibody. TREM2 expression in macrophages incubated with the CM was assessed. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p n Western blot analysis of the indicated proteins in Raw264.7 and BMDMs incubated with the indicated CM. The experiment was independently repeated three times with similar results. o Quantification of the proportion of TREM2 in Raw264.7 and BMDMs incubated with the indicated CM. n = 3 biological independent samples. p Representative multiplex immunofluorescence staining of CD68, TREM2 and FGF2 in tumors treated with PTX or Nab-PTX ( n = 3 mice per group). The experiment was independently repeated three times with similar results. Data are shown as means ± S.D. and were analyzed by two-sided unpaired Student’s t test ( b , e , h and i ) and two-sided one-way ANOVA followed by Tukey’s test ( l and o ). Source data are provided as a Source Data file.

Article Snippet: The Nab-PTX (HY-P99974) was purchased from MedChemExpress and used at a concentration of 9 mg/kg.

Techniques: Western Blot, Expressing, Incubation, Immunofluorescence, Staining, Recombinant, Multiplex Assay

Journal: Nature Communications

Article Title: Paclitaxel drives TREM2 + macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

doi: 10.1038/s41467-026-69060-5

Figure Lengend Snippet: a Overlap of RNA-seq ( n = 3) and PROMO public database analyses to predict transcription factors regulating TREM2 expression. b Correlations between FGF2 and ATF3 expression in breast cancer using TCGA databases. c qPCR analysis of Atf3 expression in the indicated cells. n = 4 (DMSO and PTX) or 3 (PBS and Nab-PTX) biological independent samples. d Western blot analysis of the indicated proteins in Py8119 cells transfected with ATF3-expressing or control vectors. The experiment was independently repeated three times with similar results. e qPCR analysis of Fgf2 expression in Py8119 cells transfected with Atf3 -expressing or control vectors. n = 3 biological independent samples. f Luciferase activity in HEK293T cells transfected with the indicated reporters and Atf3 -expressing or control vectors. n = 3 biological independent samples. g Abundance of Atf3 bound to the Trem2 promoter in Py8119 cells, as assessed by ChIP-qPCR. n = 3 biological independent samples. h ATAC-seq tracks showing the chromatin accessibility in the ATF3 loci for BT549 cells treated by PTX or Nab-PTX. n = 2 samples per group. Data are shown as means ± S.D. and were analyzed by two-sided unpaired Student’s t test ( c, e and f ) and two-sided two-way ANOVA followed by Šídák’s test ( g ). Source data are provided as a Source Data file.

Article Snippet: The Nab-PTX (HY-P99974) was purchased from MedChemExpress and used at a concentration of 9 mg/kg.

Techniques: RNA Sequencing, Expressing, Western Blot, Transfection, Control, Luciferase, Activity Assay, ChIP-qPCR

Journal: Nature Communications

Article Title: Paclitaxel drives TREM2 + macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

doi: 10.1038/s41467-026-69060-5

Figure Lengend Snippet: a Overlap of GeneCards and EDCODE public databases analyses to predict transcription factors that regulate TREM2. b Western blot analysis of the indicated proteins in BMDMs and Raw264.7 cells incubated with FGF2 (left) and with CM from Py8119 cells treated with PTX (right). The experiment was independently repeated three times with similar results. c Western blot analysis of the indicated proteins in Raw264.7 cells incubated with the indicated treatment. The experiment was independently repeated three times with similar results. d qPCR analysis of Trem2 expression in BMDMs transfected with Egr1 -expressing vectors. n = 3 biological independent samples. e Western blot analysis of TREM2 expression in BMDMs transfected with Egr1 -expressing vectors. The experiment was independently repeated three times with similar results. f Luciferase activity of HEK293T cells transfected with the indicated reporters and EGR1 -expressing or control vectors. n = 3 biological independent samples. g Abundance of EGR1 bound to the TREM2 promoter in BMDMs assessed by ChIP-qPCR. n = 3 biological independent samples. h Schematic of the Transwell assay. The first CM was collected from tumor cells with indicated treatment, and the second CM was collected from macrophages incubated with the first CM. The migration and invasion capabilities of macrophages incubated with the first CM were assessed. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p i Quantification of migration and invasion of Py8119 cells induced by BMDM CM incubated with CM from Py8119 cells treated with PTX, and BT549, SUM159, and MDA-MB-231 cells induced by THP1 CM incubated with CM from BT549, SUM159, and MDA-MB-231 cells treated with PTX (left) or Nab-PTX (right), respectively. n = 5 biological independent samples. j Cytokine array analysis of CM from BMDMs with or without TREM2. k Quantification of migration and invasion of Py8119 cells incubated with indicated proteins. n = 3 biological independent samples. l Quantification of migration and invasion of Py8119 cells induced by CM from BMDMs ( Trem2 +/+ ) with CDE-096. n = 3 biological independent samples. m Western blot analysis of EMT- stimulating proteins in BMDMs incubated with indicated proteins. The experiment was independently repeated three times with similar results. n Schematic illustration showing that FGF2 promotes ERK1/2 phosphorylation to upregulate EGR1, which increases TREM2 expression in macrophages. Upregulated TREM2 enhances the secretion of Serpin E1, HGF, CCL3, and CXCL2 from macrophages to tumor cells, facilitating tumor metastasis via EMT. Created in BioRender. Xing, Y. (2026) https://BioRender.com/nsp747p . Data are shown as means ± S.D. and were analyzed by two-sided unpaired Student’s t test ( d, f, i and l ), two-sided one-way ANOVA followed by Tukey’s test ( k ) and two-sided two-way ANOVA followed by Šídák’s test ( g ). Source data are provided as a Source Data file.

Article Snippet: The Nab-PTX (HY-P99974) was purchased from MedChemExpress and used at a concentration of 9 mg/kg.

Techniques: Western Blot, Incubation, Expressing, Transfection, Luciferase, Activity Assay, Control, ChIP-qPCR, Transwell Assay, Migration, Phospho-proteomics

Journal: Nature Communications

Article Title: Paclitaxel drives TREM2 + macrophage expansion underlying its inferior therapeutic efficacy compared to Nab-paclitaxel

doi: 10.1038/s41467-026-69060-5

Figure Lengend Snippet: PTX, but not Nab-PTX, promotes lung metastasis by inducing TREM2 + macrophage recruitment. Mechanistically, PTX enhances the ATF3-FGF2 axis in breast cancer cells; secreted FGF2 activates the EGR1–TREM2–EMT cytokine axis in macrophages. Created in BioRender. Xing, Y. (2026) https://BioRender.com/6hxlbow .

Article Snippet: The Nab-PTX (HY-P99974) was purchased from MedChemExpress and used at a concentration of 9 mg/kg.

Techniques:

Journal: Frontiers in Cell and Developmental Biology

Article Title: Vitamin D Promotes Trophoblast Cell Induced Separation of Vascular Smooth Muscle Cells in Vascular Remodeling via Induction of G-CSF

doi: 10.3389/fcell.2020.601043

Figure Lengend Snippet: Effect of G-CSF on VSMC disorganization and phenotypic switching in the CPA model. (A) G-CSF induces VSMC disorganization in the CPA model of vascular remodeling. (B) Neutralization of G-CSF in vitamin D treated PEx CM abrogates the ability to induce VSMC disorganization. (C) G-CSF induces VSMC phenotypic from a contractile to synthetic phenotype as evidenced by reduced αSMA and increased osteopontin expression. (D) Neutralization of G-CSF in vitamin D treated PEx CM abrogates the ability to induce VSMC phenotypic switching. N = 5 each group. Scale bars = 50 μm.

Article Snippet: Antibodies to human alpha smooth muscle Actin (αSMA, ab32575), osteopontin (OPN, ab69498), anti-G-CSF (ab204989), and anti-G-CSF Receptor (ab126167) were purchased from Abcam.

Techniques: Neutralization, Expressing

Journal: Frontiers in Cell and Developmental Biology

Article Title: Vitamin D Promotes Trophoblast Cell Induced Separation of Vascular Smooth Muscle Cells in Vascular Remodeling via Induction of G-CSF

doi: 10.3389/fcell.2020.601043

Figure Lengend Snippet: G-CSF induces VSMC phenotypic switching in vitro . (A) G-CSF induces VSMC invasion. (B) G-CSF increases the number of F-actin stress fibers in VMCs. Arrows denote F-actin stress fibers in a high power image. (C) Representative photomicrograph of IF staining for αSMA, osteopontin and KLF4 (red)/F-actin (green). High power inset of one cell double IF stained for KLF4 (red)/F-actin (green). IgG negative control. Note increased αSMA and KLF4, and reduced osteopontin as markers of VSMC phenotypic switching from a contractile to synthetic phenotype. N = 3 all groups. (D) Representative Western blots for αSMA, OPN, and GAPDH with corresponding quantitation for VSMCs treated with 3 ng/ml G-CSF for 24 h ( n = 10).

Article Snippet: Antibodies to human alpha smooth muscle Actin (αSMA, ab32575), osteopontin (OPN, ab69498), anti-G-CSF (ab204989), and anti-G-CSF Receptor (ab126167) were purchased from Abcam.

Techniques: In Vitro, Staining, Negative Control, Western Blot, Quantitation Assay