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 FGF2 protein (HY-P73052AF) was purchased from MedChemExpress and used with indicated concentration.

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 FGF2 protein (HY-P73052AF) was purchased from MedChemExpress and used with indicated concentration.

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 FGF2 protein (HY-P73052AF) was purchased from MedChemExpress and used with indicated concentration.

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 FGF2 protein (HY-P73052AF) was purchased from MedChemExpress and used with indicated concentration.

Techniques: