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Comprehending the mechanisms and key regulators of cancer\u2010immune crosstalk in the TME is imperative for developing efficacious immunotherapy. Through a series of in vivo CRISPR screens, we identified tumor\u2010intrinsic ITGB1 as a critical regulator of triple\u2010negative breast cancer (TNBC) development and deciphered its underlying mechanisms. Tumoral ITGB1 facilitated the establishment of pro\u2010tumorigenic TME by orchestrating tumor\u2010associated myeloid populations. Suppressing ITGB1 favored the enrichment of anti\u2010tumorigenic myeloid cells and enhanced infiltration of CD4 and CD8 T cells, culminating in superior antitumor effects. CRISPR scanning pinpointed a previously unrecognized functional domain essential for ITGB1's pro\u2010tumorigenic activity. This domain is distinct from all known ligand\u2010binding sites in ITGB1. An antibody capable of sterically blocking this domain significantly impaired TNBC progression. 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Our study uncovers a novel mechanism of TNBC development and provides a unique therapeutic strategy for targeting ITGB1 in TNBC treatment.<\/jats:p>","DOI":"10.1002\/advs.202513672","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T18:35:43Z","timestamp":1770143743000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ITGB1 Regulates Triple\u2010Negative Breast Cancer Development by Modulating the Tumor Microenvironment"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1764-7543","authenticated-orcid":false,"given":"Nuozi","family":"Song","sequence":"first","affiliation":[{"name":"Department of Immuno\u2010Oncology Beckman Research Institute City of Hope  Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immuno\u2010Oncology 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