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Journal: Cellular Oncology
Article Title: Targeting senescence-like tumor-associated macrophages sensitizes chemotherapy in triple-negative breast cancer
doi: 10.1007/s13402-026-01197-3
Figure Lengend Snippet: Senescence-like TAMs are induced upon chemotherapy in vivo. (A) CD163⁺ TAMs were isolated from human breast cancer tissue obtained via needle biopsy (pre-treatment) and surgical resection (post-neoadjuvant chemotherapy). Isolated TAMs underwent proteomic profiling using LC-MS/MS. The dataset is downloaded from the PRIDE repository under accession PXD022673. (B) Gene Set Enrichment Analysis (GSEA) of proteomic data highlights significantly altered biological functions in TAMs following neoadjuvant chemotherapy. (C) GSEA reveals significant upregulation of cellular senescence signatures in TAMs isolated from ADM-treated orthotopic 4T1 tumors, compared to PBS-treated controls. The dataset is downloaded from the PRIDE repository under accession PXD022674. (D) IF analysis of p16 + F4/80 + and p21 + F4/80 + TAMs isolated from treatment-naïve and ADM-treated tumors ( n = 5). Scale bar, 50 μm. (E) Real-time qPCR analysis of senescence-related genes ( Cdkn2a , Cdkn1a , and Trp53 ) in TAMs isolated from treatment-naïve and ADM-treated tumors ( n = 5). (F) Western blotting analysis of senescence markers (p16 and p21) in TAMs isolated from treatment-naïve and ADM-treated tumors ( n = 5). (G) ELISA quantification of senescence-associated secretory phenotype (SASP) markers (IL-1α, IL-6, CXCL1, TNF-α) in conditioned media from TAMs isolated from orthotopic 4T1 tumors treated with control or ADM ( n = 5). For statistical analyses, an unpaired two-tailed t-test was used. * P < 0.05, ** P < 0.01
Article Snippet:
Techniques: In Vivo, Isolation, Liquid Chromatography with Mass Spectroscopy, Western Blot, Enzyme-linked Immunosorbent Assay, Control, Two Tailed Test
Journal: Cellular Oncology
Article Title: Targeting senescence-like tumor-associated macrophages sensitizes chemotherapy in triple-negative breast cancer
doi: 10.1007/s13402-026-01197-3
Figure Lengend Snippet: IL-6, a key factor of SASP, mediates chemoresistance in TNBC. (A) Viability of 4T1 tumor cells treated for 48 h with conditioned medium (CM) from TAMs isolated from PBS- or ADM-treated orthotopic 4T1 tumors, with/without neutralizing antibodies against SASP factors (IL-1α, IL-6, CXCL1, and TNF-α). Viability measured by CCK-8 assay (OD 450 nm). (B) CCK-8 assay showing the viability of 4T1 tumor cells upon treatment of recombinant IL-6 for 48 h. (C) ELISA analysis of IL-6 levels in TEC, CAF, or TAMs isolated from treatment-naïve or ADM-treated tumors ( n = 5). (D) Schematic model showing ADM and anti-IL-6 in the 4T1 orthotopic tumor model. (E) Tumor growth curves and tumor biopsies following administration of PBS, ADM, anti-IL-6, and ADM + anti-IL-6 combination therapy ( n = 5 mice per group). (F) Real-time qPCR analysis of drug resistance- and stemness-associated genes ( Abcb1 , Abcc1 , Cd44 , Aldh1a1 , and Prom1 ) in 4T1 cells with indicated treatments; tocilizumab at 10 µg/ml and Stattic at 5 µM. For statistical analyses, two-way ANOVA with Tukey’s multiple comparisons ( B ), unpaired two-tailed t-test ( D ) or one-way ANOVA followed by Tukey’s post hoc test ( E ) was used. ** P < 0.01, *** P < 0.001, and **** P < 0.0001
Article Snippet:
Techniques: Isolation, CCK-8 Assay, Recombinant, Enzyme-linked Immunosorbent Assay, Two Tailed Test
Journal: Cellular Oncology
Article Title: Targeting senescence-like tumor-associated macrophages sensitizes chemotherapy in triple-negative breast cancer
doi: 10.1007/s13402-026-01197-3
Figure Lengend Snippet: Mechanism model. In the TNBC microenvironment, chemotherapy induces cellular senescence in TAMs. These senescence-like TAMs develop a senescence-associated secretory phenotype (SASP), prominently IL-6 secretion. IL-6 signals through the IL-6R-STAT3 axis in TNBC cells, thus inducing genes related to drug resistance (e.g., ABC transporters) and cancer stemness ( Cd44 , Aldh1a1 , and Prom1 ), ultimately driving therapeutic resistance
Article Snippet:
Techniques: