{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T04:40:54Z","timestamp":1776660054021,"version":"3.51.2"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473997"],"award-info":[{"award-number":["82473997"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073919"],"award-info":[{"award-number":["82073919"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cancer stem cells (CSCs) contribute to an immunosuppressive microenvironment through complex mechanisms and tumor\u2010immune interactions. However, the key determinants of CSC characteristics in driving tumor progression, immune suppression, and response to ICIs remain unclear and require systematic investigation. This study developed a quantitative systems pharmacology (QSP) model covering various CSC properties, thereby capturing the temporal dynamics and CSC\u2010immune interactions in triple\u2010negative breast cancer (TNBC). Using the unified longitudinal dataset of tumor growth, CSC frequency, and immune cell dynamics that we obtained from BALB\/c mice bearing wild\u2010type or\n                    <jats:italic>Cd274<\/jats:italic>\n                    \u2010knockout 4T1 cells under various inoculation conditions, which provides multi\u2010dimensional insights into CSC\u2010related biology, the QSP model was calibrated and validated. Simulations and sensitivity analysis indicated that TNBC tumors with strong stemness exhibited significantly accelerated tumor growth and reduced infiltration of cytotoxic immune cells such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. These were associated with CSCs' enhanced self\u2010renewal capacity, stemness maintenance, secretion of transforming growth factor beta (TGF\u2010\u03b2) and vascular endothelial growth factor (VEGF), and PD\u20101\/PD\u2010L1\u2013mediated immunosuppression. ICIs showed minimal efficacy in tumors with enhanced stemness, which was also linked to the aforementioned characteristics. Both the administration sequence and initiation timing of ICIs differentially influenced the therapeutic outcomes. These findings elucidate the roles of CSCs in TNBC progression, tumor immunity, and ICI efficacy while identifying the key underlying CSC characteristics, suggesting the potential value of assessing CSC biomarkers or abundance before ICI treatment and support the development of ICIs and anti\u2010CSC combination therapies.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70245","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T06:06:26Z","timestamp":1775541986000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative\n                    <scp>QSP<\/scp>\n                    Modeling of Cancer Stem Cells in Triple\u2010Negative Breast Cancer: Impacts on Tumor Immunity and Response to Immune Checkpoint Inhibitors"],"prefix":"10.1002","volume":"15","author":[{"given":"Junsheng","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, School of 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