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Herein, we identified that SOX30 is significantly upregulated in TNBC and correlates with poor clinical prognosis. Functionally, SOX30 specifically drives TNBC metastasis and activates the TNFR2\u2010mediated downstream NF\u2010\u03baB signaling cascade. Mass cytometry profiling of the tumor immune microenvironment revealed that SOX30 facilitates the recruitment of tumor\u2010associated macrophages (TAMs) within pulmonary metastases, a finding corroborated by flow cytometric quantification. Mechanistically, downstream pathway analyses identified that SOX30 induces activation of the TNFR2\u2013NF\u2010\u03baB axis and concurrently upregulates expression of the chemokine CCL20. Therapeutic intervention with CCL20 neutralizing antibodies or small\u2010molecule CCR6 inhibitors effectively attenuated metastatic progression and abrogated TAM infiltration. Strikingly, combinatorial blockade using the TNFR2 inhibitor etanercept together with a CCR6 inhibitor exhibited superior anti\u2010metastatic efficacy relative to control treatments. Collectively, our findings delineate a novel oncogenic SOX30\u2013TNFR2\u2013NF\u2010\u03baB\u2013CCL20\/CCR6 axis driving TNBC metastasis. These results establish SOX30 as a promising prognostic biomarker and a potential therapeutic target for anti\u2010metastatic strategies in TNBC.<\/jats:p>","DOI":"10.1002\/advs.77690","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:32:41Z","timestamp":1789018361000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SOX30 Facilitates Triple\u2010Negative Breast Cancer Metastasis via TNFR2\u2013NF\u2010\u03baB Signaling and Tumor Microenvironment Remodeling"],"prefix":"10.1002","author":[{"given":"Pingping","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Southwest Hospital Army Medical University  Chongqing People's Republic of China"},{"name":"Key Laboratory of Chongqing Health Commission for Minimally Invasive and Precise Diagnosis  Chongqing People's Republic of 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