{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:15Z","timestamp":1787026515235,"version":"build-2736575974"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Triple-negative breast cancer (TNBC) is defined by the absence of estrogen, progesterone, and HER2 receptor expression. A critical challenge in managing TNBC is its high concentration of cancer stem cells (CSCs), which drives chemotherapy resistance and correlates with poor patient survival. In normal physiology, stem cell pluripotency and differentiation are governed by core transcription factors (such as Oct4, Sox2, Nanog, Klf4, and c-Myc) alongside key signaling networks, including the Notch, Wnt\/\u03b2-catenin, and Sonic Hedgehog (Shh) pathways. During carcinogenesis, aberrant activation of these regulators in TNBC not only promotes the self-renewal of tumor cells but also actively facilitates immune evasion. Specifically, overexpressed pluripotency transcription factors enable cancer cells to downregulate antigen presentation molecules (e.g., MHC class I) and secrete immunomodulatory cytokines. Concurrently, dysregulated signaling, such as the Wnt\/\u03b2-catenin pathway, inhibits dendritic cell maturation and recruits Myeloid-Derived Suppressor Cells (MDSCs) and regulatory T cells (Tregs) into the tumor microenvironment, thereby blunting the anti-tumor T cell response. This review examines the role of key pluripotency regulators in TNBC-mediated immune evasion, highlighting emerging immunotherapeutic strategies targeting these networks and summarizing current clinical research.<\/jats:p>","DOI":"10.3389\/fgene.2026.1771872","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T22:10:11Z","timestamp":1776895811000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The role of pluripotency regulators in triple-negative breast cancer immune response"],"prefix":"10.3389","volume":"17","author":[{"given":"Carolina","family":"L\u00f3pez-Santana","sequence":"first","affiliation":[{"name":"Cell Therapy, Immunology and Clinical Oncology Research Group (GIIOC), Fundaci\u00f3n Salud de Los Andes","place":["Bogot\u00e1, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Mendez-Rivera","sequence":"additional","affiliation":[{"name":"Cell Therapy, Immunology and Clinical Oncology Research Group (GIIOC), Fundaci\u00f3n Salud de Los Andes","place":["Bogot\u00e1, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bernal-Est\u00e9vez","sequence":"additional","affiliation":[{"name":"Cell Therapy, Immunology and Clinical Oncology Research Group (GIIOC), Fundaci\u00f3n Salud de Los Andes","place":["Bogot\u00e1, Colombia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1002\/jcp.30529","article-title":"TGF-Beta signaling: a recap of SMAD-independent and SMAD-dependent pathways","volume":"237","author":"Aashaq","year":"2022","journal-title":"J. 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