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Here, we systematically assessed the cellular differentiation status of human breast cancer cells using single-cell atlases and identified a distinct population of immature basal-like cancer cells marked by\n                    <jats:italic toggle=\"yes\">BCL11B<\/jats:italic>\n                    . Notably, higher levels of\n                    <jats:italic toggle=\"yes\">BCL11B<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    cancer cells are significantly associated with early relapse in patients with breast cancer who received chemotherapy. Functioning as a central regulator, B-cell lymphoma\/leukemia 11B (BCL11B) delineates an immature cell state that preferentially transitions to a drug-resistant persister state during treatment through multiple preexisting and adaptive drug resistance programs. The cytokine tumor necrosis factor\u2013\u03b1 (TNF\u03b1) is revealed as a natural inhibitor of BCL11B and can directly reverse the emergence of chemoresistant persister cells. Therefore, we identify BCL11B as an unappreciated predeterminant of drug response and a therapeutic target for a subset of patients with breast cancer at high risk of developing chemoresistance.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aec5436","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:58:47Z","timestamp":1788976727000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["BCL11B predetermines a persister state in breast cancer that is reversed by TNF\u03b1"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8793-9884","authenticated-orcid":true,"given":"Zhen","family":"Qi","sequence":"first","affiliation":[{"name":"Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA 94305, 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