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To address this, we aim to construct a novel prognostic framework based on tumor-immune interactions. Through integrative analysis of single-cell RNA sequencing data from 30 TNBC samples (106,132 cells), we identify key tumor expression metaprograms and uncover their interaction with an immunosuppressive dendritic-cell subset, a process associated with the NECTIN1\u2013NECTIN4 axis. Leveraging these interactions, we developed and validated two immunological prognostic models using multi-cohort transcriptomic data, including the stress response tumor cell and pDC_CLEC4C prognostic model (SPSM) and the immune response tumor cell and pDC_CLEC4C prognostic model (IPSM). These models effectively stratified TNBC patients into distinct risk groups, with the low-risk group characterized by an immunologically active microenvironment and elevated expression of immune checkpoint genes, suggesting a potential responsiveness to immunotherapy. Furthermore, we identified several potential therapeutic agents, including imatinib and bortezomib. Collectively, our dual-model framework provides a tool for risk stratification, offers translational insights for precision treatment, and presents new directions for understanding TNBC heterogeneity and therapeutic development.<\/jats:p>","DOI":"10.3390\/ijms27031494","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T10:03:29Z","timestamp":1770113009000},"page":"1494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Immunological Prognostic Models for Risk Stratification and Treatment Insights in Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"27","author":[{"given":"Shihua","family":"Lin","sequence":"first","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjiu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Biomedical Information and Engineering, Hainan Medical University, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenzhen","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Biomedical Information and Engineering, Hainan Medical University, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxuan","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8195-1993","authenticated-orcid":false,"given":"Menoudji Djetoyom","family":"Patrice","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3709-3656","authenticated-orcid":false,"given":"Yunpeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"},{"name":"College of Biomedical Information and Engineering, Hainan Medical University, Haikou 571199, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/ame2.12445","article-title":"Single-cell analysis of tumor microenvironment and cell adhesion reveals that interleukin-1 beta promotes cancer cell proliferation in breast cancer","volume":"7","author":"Wang","year":"2024","journal-title":"Anim. 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