{"id":"doi:10.1016/j.tranon.2026.103032","kind":"article","title":"Siglec-15 promotes a feed-forward loop between TNBC cells and macrophages via the NF-κB/DcR3/CCL18/STAT3 axis","authors":["Wang S","Wang HQ","Zhao H","Zhao R","Zhao P","Mu Q"],"author_count":6,"year":2026,"published":"2026-09-18","venue":"Translational oncology","cited_by":0,"doi":"10.1016/j.tranon.2026.103032","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.tranon.2026.103032","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.tranon.2026.103032","updated":null,"pmid":"42759405","pmcid":"PMC13625897","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13625897/pdf","abstract":"M2-like tumor-associated macrophages (TAMs), recognized as a significant risk factor in tumor progression, play a crucial role in the tumor microenvironment. While Sialic acid binding Ig like Lectin 15 (Siglec-15), an well-characterized immune-checkpoint inhibitor, has been demonstrated to impact immunotherapy response and tumor progression, its role in TMAs-mediated tumor progression remains largely unclear. In this study, we demonstrated that the high expression of Siglec-15 in triple-negative breast cancer (TNBC) acts as a pivotal driver of the interaction between tumor cells and macrophages. TNBC cells with overexpressed Siglec-15 can induce the polarization of macrophages into CC chemokine ligand 18 (CCL18) + M2 macrophages and recruit macrophages. Furthermore, CCL18⁺ M2 TAMs can directly facilitate the malignant behaviors of TNBC cells. Mechanistically, they secrete CCL18, which promotes the expression of Siglec-15 via the phosphorylation of signal transducer and activator of transcription 3 (STAT3), thereby indirectly accelerating tumor progression. Molecular biochemical assays, including RNA sequencing on TNBC cells with overexpressed Siglec-15 and capillary reverse-phase liquid chromatography (LC)-tandem mass spectrometry (MS/MS) of the cell supernatant, demonstrated Siglec-15 upregulated the expression of Decoy receptor 3 (DcR3) in macrophages through Nuclear factor-kappa B (NF-κB) pathway. In summary, this study reveals a novel Siglec-15-mediated positive feed-forward loop between TNBC cells and macrophages, which relies on the NF-κB/DcR3/CCL18/STAT3 signaling axis to facilitate TNBC progression..","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Siglec-15 promotes a feed-forward loop between TNBC cells and macrophages via the NF-κB/DcR3/CCL18/STAT3 axis\" by Wang S, Wang HQ, Zhao H et al., https://doi.org/10.1016/j.tranon.2026.103032, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"cancer-immunotherapy","name":"Cancer Immunotherapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}