{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:13:14Z","timestamp":1786122794101,"version":"build-2736575974"},"reference-count":196,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"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. Oncol."],"abstract":"<jats:p>The clinical success of immune checkpoint blockade and adoptive T-cell therapies has cemented a T-cell-centric paradigm in cancer immunology, inadvertently overshadowing the humoral arm of adaptive immunity. However, mounting evidence now demands a recalibration of this view, particularly in breast cancer, where tumor-infiltrating B cells (TIL-Bs), including terminally differentiated plasma cells, and the antibodies they produce emerge as active architects of the tumor microenvironment rather than passive bystanders. In this Review, we synthesize current insights into B-cell biology across the breast cancer ecosystem, from developmental ontogeny to functional specialization within tertiary lymphoid structures (TLSs). We dissect the dualistic nature of TIL-Bs: on one hand, clonally expanded, class-switched plasma cells and TLS-associated germinal center reactions drive potent anti-tumor immunity through antibody-dependent cytotoxicity, antigen presentation, and T-cell collaboration; on the other hand, regulatory B cells, atypical memory subsets, and pathogenic antibody isotypes foster immunosuppression, angiogenesis, and metastatic dissemination. We further examine the prognostic and predictive value of B-cell metrics across molecular subtypes, highlighting their association with response to neoadjuvant chemotherapy, anti-HER2 therapy, and immune checkpoint inhibition, especially in triple-negative and HER2-positive disease. Finally, we discuss emerging therapeutic strategies to harness anti-tumor B-cell responses while addressing the significant challenges of functional stratification, biomarker standardization, and the translation of preclinical insights into clinical benefit. Integrating B-cell function, rather than mere quantity, into next-generation pathological reporting and adaptive trial designs represents an essential frontier for precision oncology in breast cancer.<\/jats:p>","DOI":"10.3389\/fonc.2026.1883381","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T12:18:43Z","timestamp":1786105123000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["B-cells in breast cancer: current insights and challenges"],"prefix":"10.3389","volume":"16","author":[{"given":"Bo","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, Jilin Cancer Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Jilin Cancer Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Jilin Cancer Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Jilin Cancer Hospital","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1186\/s13046-019-1266-0","article-title":"Advances in cancer immunotherapy 2019 - latest trends","volume":"38","author":"Kruger","year":"2019","journal-title":"J Exp Clin Cancer Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2147\/bctt.S588323","article-title":"Immune checkpoint blockade and emerging combination platforms in breast cancer: a 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