{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T10:13:19Z","timestamp":1793527999364,"version":"4.5.0"},"reference-count":74,"publisher":"American Association for Cancer Research (AACR)","issue":"7","funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG059244"],"award-info":[{"award-number":["AG059244"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["CA217208"],"award-info":[{"award-number":["CA217208"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["BC181712"],"award-info":[{"award-number":["BC181712"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["P30CA091842"],"award-info":[{"award-number":["P30CA091842"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["CA113275"],"award-info":[{"award-number":["CA113275"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["CA271721"],"award-info":[{"award-number":["CA271721"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017618","name":"Division of Diabetes, Endocrinology, and Metabolic Diseases","doi-asserted-by":"publisher","award":["DK122633"],"award-info":[{"award-number":["DK122633"]}],"id":[{"id":"10.13039\/100017618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["CA275212"],"award-info":[{"award-number":["CA275212"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["CA21720605"],"award-info":[{"award-number":["CA21720605"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["CA21720605"],"award-info":[{"award-number":["CA21720605"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["CA223758"],"award-info":[{"award-number":["CA223758"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["CA254060"],"award-info":[{"award-number":["CA254060"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM7200-49"],"award-info":[{"award-number":["GM7200-49"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>The tumor microenvironment (TME) profoundly influences tumorigenesis, with gene expression in the breast TME capable of predicting clinical outcomes. The TME is complex and includes distinct cancer-associated fibroblast (CAF) subtypes whose contribution to tumorigenesis remains unclear. Here, we identify a subset of myofibroblast CAFs (myCAF) that are senescent (senCAF) in mouse and human breast tumors. Utilizing the MMTV-PyMT;INK-ATTAC (INK) mouse model, we found that senCAF-secreted extracellular matrix specifically limits natural killer (NK) cell cytotoxicity to promote tumor growth. Genetic or pharmacologic senCAF elimination unleashes NK cell killing, restricting tumor growth. Finally, we show that senCAFs are present in HER2+, ER+, and triple-negative breast cancer and in ductal carcinoma in situ (DCIS) where they predict tumor recurrence. Together, these findings demonstrate that senCAFs are potently tumor promoting and raise the possibility that targeting them by senolytic therapy could restrain breast cancer development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>senCAFs limit NK cell-mediated killing, thereby contributing to breast cancer progression. Thus, targeting senCAFs could be a clinically viable approach to limit tumor progression.<\/jats:p>\n                    <jats:p>See related article by Belle et al., p. 1324.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-23-0426","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T10:02:32Z","timestamp":1714384952000},"page":"1302-1323","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":181,"title":["Senescent CAFs Mediate Immunosuppression and Drive Breast Cancer Progression"],"prefix":"10.1158","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7987-6360","authenticated-orcid":false,"given":"Jiayu","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri. 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8758-0030","authenticated-orcid":false,"given":"John M.","family":"Baer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2452-0962","authenticated-orcid":false,"given":"Douglas V.","family":"Faget","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri. 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9827-2757","authenticated-orcid":false,"given":"Vasilios A.","family":"Morikis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-1829","authenticated-orcid":false,"given":"Qihao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri. 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1000-5273","authenticated-orcid":false,"given":"Anupama","family":"Melam","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri. 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1219-4311","authenticated-orcid":false,"given":"Ana Paula","family":"Delgado","sequence":"additional","affiliation":[{"name":"Graduate Program in Genetics, Stony Brook University, Stony Brook, New York. 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8696-0074","authenticated-orcid":false,"given":"Xianmin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri. 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7091-7360","authenticated-orcid":false,"given":"Satarupa Mullick","family":"Bagchi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri. 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-9792","authenticated-orcid":false,"given":"Jad I.","family":"Belle","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7107-1879","authenticated-orcid":false,"given":"Edward","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri. 1"},{"name":"Medical Scientist Training Program, Washington University School of Medicine, St. Louis, Missouri. 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9341-7571","authenticated-orcid":false,"given":"Michael","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri. 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7101-5582","authenticated-orcid":false,"given":"Deborah J.","family":"Veis","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri. 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5130-5969","authenticated-orcid":false,"given":"Erik S.","family":"Knudsen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York. 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4538-1145","authenticated-orcid":false,"given":"Agnieszka K.","family":"Witkiewicz","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York. 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2769-1932","authenticated-orcid":false,"given":"Scott","family":"Powers","sequence":"additional","affiliation":[{"name":"Department of Pathology and Cancer Center, Renaissance School of Medicine, Stony Brook, New York. 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7568-8151","authenticated-orcid":false,"given":"Gregory D.","family":"Longmore","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. 2"},{"name":"ICCE Institute, Washington University School of Medicine, St. Louis, Missouri. 8"},{"name":"Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri. 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3655-5783","authenticated-orcid":false,"given":"David G.","family":"DeNardo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. 2"},{"name":"ICCE Institute, Washington University School of Medicine, St. Louis, Missouri. 8"},{"name":"Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri. 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2260-9576","authenticated-orcid":false,"given":"Sheila A.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri. 1"},{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. 2"},{"name":"ICCE Institute, Washington University School of Medicine, St. Louis, Missouri. 8"},{"name":"Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri. 9"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"key":"2026041320320308200_bib1","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nm1764","article-title":"Stromal gene expression predicts clinical outcome in breast cancer","volume":"14","author":"Finak","year":"2008","journal-title":"Nat Med"},{"key":"2026041320320308200_bib2","doi-asserted-by":"crossref","first-page":"166","DOI":"10.2741\/3613","article-title":"Cancer-associated fibroblasts (CAFs) in tumor microenvironment","volume":"15","author":"Xing","year":"2010","journal-title":"Front Biosci"},{"key":"2026041320320308200_bib3","doi-asserted-by":"crossref","first-page":"6841","DOI":"10.3748\/wjg.v22.i30.6841","article-title":"Cancer-associated fibroblasts in hepatocellular carcinoma","volume":"22","author":"Kubo","year":"2016","journal-title":"World J Gastroenterol"},{"key":"2026041320320308200_bib4","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/s43018-022-00411-z","article-title":"Cancer-associated fibroblasts in the single-cell era","volume":"3","author":"Lavie","year":"2022","journal-title":"Nat Cancer"},{"key":"2026041320320308200_bib5","doi-asserted-by":"crossref","first-page":"5150","DOI":"10.1038\/s41467-018-07582-3","article-title":"Spatially and functionally distinct subclasses of breast cancer associated fibroblasts revealed by single cell RNA sequencing","volume":"9","author":"Bartoschek","year":"2018","journal-title":"Nat Commun"},{"key":"2026041320320308200_bib6","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1084\/jem.20162024","article-title":"Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer","volume":"214","author":"\u00d6hlund","year":"2017","journal-title":"J Exp Med"},{"key":"2026041320320308200_bib7","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1158\/2159-8290.CD-19-0094","article-title":"Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts","volume":"9","author":"Elyada","year":"2019","journal-title":"Cancer Discov"},{"key":"2026041320320308200_bib8","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.3390\/cancers12051307","article-title":"Single-cell transcriptomic analysis of tumor-derived fibroblasts and normal tissue-resident fibroblasts reveals fibroblast heterogeneity in breast cancer","volume":"12","author":"Sebastian","year":"2020","journal-title":"Cancers"},{"key":"2026041320320308200_bib9","doi-asserted-by":"crossref","first-page":"e129212","DOI":"10.1172\/jci.insight.129212","article-title":"Cellular heterogeneity during mouse pancreatic ductal adenocarcinoma progression at single-cell resolution","volume":"5","author":"Hosein","year":"2019","journal-title":"JCI Insight"},{"key":"2026041320320308200_bib10","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41586-022-05272-1","article-title":"LRRC15+ myofibroblasts dictate the stromal setpoint to suppress tumour immunity","volume":"611","author":"Krishnamurty","year":"2022","journal-title":"Nature"},{"key":"2026041320320308200_bib11","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1158\/2159-8290.CD-18-0710","article-title":"IL1-induced JAK\/STAT signaling is antagonized by TGF\u03b2 to Shape CAF heterogeneity in pancreatic ductal adenocarcinoma","volume":"9","author":"Biffi","year":"2019","journal-title":"Cancer Discov"},{"key":"2026041320320308200_bib12","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2019104063","article-title":"Stromal cell diversity associated with immune evasion in human triple-negative breast cancer","volume":"39","author":"Wu","year":"2020","journal-title":"EMBO J"},{"key":"2026041320320308200_bib13","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/s41588-021-00911-1","article-title":"A single-cell and spatially resolved atlas of human breast cancers","volume":"53","author":"Wu","year":"2021","journal-title":"Nat Genet"},{"key":"2026041320320308200_bib14","doi-asserted-by":"crossref","first-page":"11762","DOI":"10.1038\/ncomms11762","article-title":"Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis","volume":"7","author":"Ruhland","year":"2016","journal-title":"Nat Commun"},{"key":"2026041320320308200_bib15","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/s41568-019-0156-2","article-title":"Unmasking senescence: context-dependent effects of SASP in cancer","volume":"19","author":"Faget","year":"2019","journal-title":"Nat Rev Cancer"},{"key":"2026041320320308200_bib16","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1158\/2159-8290.CD-13-0743","article-title":"p38MAPK plays a crucial role in stromal-mediated tumorigenesis","volume":"4","author":"Alspach","year":"2014","journal-title":"Cancer Discov"},{"key":"2026041320320308200_bib17","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev-pathol-121808-102144","article-title":"The senescence-associated secretory phenotype: the dark side of tumor suppression","volume":"5","author":"Copp\u00e9","year":"2010","journal-title":"Annu Rev Pathol"},{"key":"2026041320320308200_bib18","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/nature05529","article-title":"Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas","volume":"445","author":"Xue","year":"2007","journal-title":"Nature"},{"key":"2026041320320308200_bib19","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1158\/2159-8290.CD-22-0523","article-title":"Cellular senescence is immunogenic and promotes antitumor immunity","volume":"13","author":"Marin","year":"2023","journal-title":"Cancer Discov"},{"key":"2026041320320308200_bib20","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1158\/2159-8290.CD-22-0528","article-title":"Senescence rewires microenvironment sensing to facilitate antitumor immunity","volume":"13","author":"Chen","year":"2023","journal-title":"Cancer Discov"},{"key":"2026041320320308200_bib21","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1158\/0008-5472.CAN-05-1716","article-title":"The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms","volume":"66","author":"Bavik","year":"2006","journal-title":"Cancer Res"},{"key":"2026041320320308200_bib22","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.1158\/0008-5472.CAN-06-3452","article-title":"Senescent human fibroblasts increase the early growth of xenograft tumors via matrix metalloproteinase secretion","volume":"67","author":"Liu","year":"2007","journal-title":"Cancer Res"},{"key":"2026041320320308200_bib23","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1126\/science.aas9090","article-title":"NK cell\u2013mediated cytotoxicity contributes to tumor control by a cytostatic drug combination","volume":"362","author":"Ruscetti","year":"2018","journal-title":"Science"},{"key":"2026041320320308200_bib24","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.tcb.2018.02.001","article-title":"Hallmarks of cellular senescence","volume":"28","author":"Hernandez-Segura","year":"2018","journal-title":"Trends Cell Biol"},{"key":"2026041320320308200_bib25","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.ajpath.2011.05.043","article-title":"Association of RB\/p16-pathway perturbations with DCIS recurrence","volume":"179","author":"Witkiewicz","year":"2011","journal-title":"Am J Pathol"},{"key":"2026041320320308200_bib26","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1158\/2159-8290.CD-22-0907","article-title":"p38MAPKa stromal reprogramming sensitizes metastatic breast cancer to immunotherapy","volume":"13","author":"Faget","year":"2023","journal-title":"Cancer Discov"},{"key":"2026041320320308200_bib27","doi-asserted-by":"crossref","first-page":"5618","DOI":"10.1158\/0008-5472.CAN-18-0234","article-title":"Inhibition of the stromal p38MAPK\/MK2 pathway limits breast cancer metastases and chemotherapy-induced bone loss","volume":"78","author":"Murali","year":"2018","journal-title":"Cancer Res"},{"key":"2026041320320308200_bib28","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s41467-021-27729-z","article-title":"Zero-preserving imputation of single-cell RNA-seq data","volume":"13","author":"Linderman","year":"2022","journal-title":"Nat Commun"},{"key":"2026041320320308200_bib29","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nature12347","article-title":"Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome","volume":"499","author":"Yoshimoto","year":"2013","journal-title":"Nature"},{"key":"2026041320320308200_bib30","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1038\/nm1518","article-title":"Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells","volume":"12","author":"Loser","year":"2006","journal-title":"Nat Med"},{"key":"2026041320320308200_bib31","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.ccell.2018.01.011","article-title":"Fibroblast heterogeneity and immunosuppressive environment in human breast cancer","volume":"33","author":"Costa","year":"2018","journal-title":"Cancer Cell"},{"key":"2026041320320308200_bib32","doi-asserted-by":"crossref","first-page":"5002","DOI":"10.3390\/ijms20205002","article-title":"TGF-\u03b2 signaling in cellular senescence and aging-related pathology","volume":"20","author":"Tominaga","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2026041320320308200_bib33","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/jmcb\/mjr033","article-title":"TGF-\u03b2: the sword, the wand, and the shield of FOXP3+ regulatory T cells","volume":"4","author":"Tran","year":"2012","journal-title":"J Mol Cell Biol"},{"key":"2026041320320308200_bib34","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/nri2808","article-title":"The polarization of immune cells in the tumour environment by TGF\u03b2","volume":"10","author":"Flavell","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"2026041320320308200_bib35","doi-asserted-by":"crossref","first-page":"e22842","DOI":"10.1371\/journal.pone.0022842","article-title":"Human Tumour immune evasion via TGF-\u03b2 blocks NK cell activation but not survival allowing therapeutic restoration of antitumour activity","volume":"6","author":"Wilson","year":"2011","journal-title":"PLoS One"},{"key":"2026041320320308200_bib36","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/j.cell.2017.07.049","article-title":"SnapShot: cellular senescence pathways","volume":"170","author":"Mart\u00ednez-Zamudio","year":"2017","journal-title":"Cell"},{"key":"2026041320320308200_bib37","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1474-9726.2006.00199.x","article-title":"Senescence-associated \u03b2-galactosidase is lysosomal \u03b2-galactosidase","volume":"5","author":"Lee","year":"2006","journal-title":"Aging Cell"},{"key":"2026041320320308200_bib38","doi-asserted-by":"crossref","first-page":"5975","DOI":"10.1038\/onc.2008.213","article-title":"Critical pathways in cellular senescence and immortalization revealed by gene expression profiling","volume":"27","author":"Fridman","year":"2008","journal-title":"Oncogene"},{"key":"2026041320320308200_bib39","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41388-020-01560-0","article-title":"Insights from transgenic mouse models of PyMT-induced breast cancer: recapitulating human breast cancer progression in vivo","volume":"40","author":"Attalla","year":"2021","journal-title":"Oncogene"},{"key":"2026041320320308200_bib40","doi-asserted-by":"crossref","first-page":"11190","DOI":"10.1038\/ncomms11190","article-title":"Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL","volume":"7","author":"Yosef","year":"2016","journal-title":"Nat Commun"},{"key":"2026041320320308200_bib41","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nature10600","article-title":"Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders","volume":"479","author":"Baker","year":"2011","journal-title":"Nature"},{"key":"2026041320320308200_bib42","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nature16932","article-title":"Naturally occurring p16Ink4a-positive cells shorten healthy lifespan","volume":"530","author":"Baker","year":"2016","journal-title":"Nature"},{"key":"2026041320320308200_bib43","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1172\/JCI95149","article-title":"Strategies targeting cellular senescence","volume":"128","author":"Ovadya","year":"2018","journal-title":"J Clin Invest"},{"key":"2026041320320308200_bib44","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1136\/gutjnl-2020-321112","article-title":"Senolytic elimination of Cox2-expressing senescent cells inhibits the growth of premalignant pancreatic lesions","volume":"71","author":"Kolodkin-Gal","year":"2022","journal-title":"Gut"},{"key":"2026041320320308200_bib45","doi-asserted-by":"crossref","first-page":"12072","DOI":"10.1073\/pnas.211053698","article-title":"Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging","volume":"98","author":"Krtolica","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026041320320308200_bib46","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12979-020-00187-9","article-title":"Role of immune cells in the removal of deleterious senescent cells","volume":"17","author":"Kale","year":"2020","journal-title":"Immun Ageing"},{"key":"2026041320320308200_bib47","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3389\/fimmu.2018.00014","article-title":"Recent Advances in targeting CD8 T-cell immunity for more effective cancer immunotherapy","volume":"9","author":"Durgeau","year":"2018","journal-title":"Front Immunol"},{"key":"2026041320320308200_bib48","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1158\/2326-6066.CIR-16-0193","article-title":"Regulatory T cells: differentiation and function","volume":"4","author":"Plitas","year":"2016","journal-title":"Cancer Immunol Res"},{"key":"2026041320320308200_bib49","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/ni1437","article-title":"Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3","volume":"8","author":"Williams","year":"2007","journal-title":"Nat Immunol"},{"key":"2026041320320308200_bib50","doi-asserted-by":"crossref","first-page":"5488","DOI":"10.1182\/blood-2008-10-187179","article-title":"Maturation of mouse NK cells is a 4-stage developmental program","volume":"113","author":"Chiossone","year":"2009","journal-title":"Blood"},{"key":"2026041320320308200_bib51","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/j.1365-2567.2011.03446.x","article-title":"CD11b and CD27 reflect distinct population and functional specialization in human natural killer cells","volume":"133","author":"Fu","year":"2011","journal-title":"Immunology"},{"key":"2026041320320308200_bib52","doi-asserted-by":"crossref","first-page":"100262","DOI":"10.1016\/j.xpro.2020.100262","article-title":"Flow cytometry-based ex vivo murine NK cell cytotoxicity assay","volume":"2","author":"Wong","year":"2021","journal-title":"STAR Protoc"},{"key":"2026041320320308200_bib53","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-019-0052-1","article-title":"NK cells for cancer immunotherapy","volume":"19","author":"Shimasaki","year":"2020","journal-title":"Nat Rev Drug Discov"},{"key":"2026041320320308200_bib54","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/cmi.2015.42","article-title":"The breast tumor microenvironment alters the phenotype and function of natural killer cells","volume":"13","author":"Krneta","year":"2016","journal-title":"Cell Mol Immunol"},{"key":"2026041320320308200_bib55","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using CellChat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat Commun"},{"key":"2026041320320308200_bib56","doi-asserted-by":"crossref","first-page":"102246","DOI":"10.1016\/j.coi.2022.102246","article-title":"Extracellular matrix-natural killer cell interactome: an uncharted territory in health and disease","volume":"78","author":"Vyas","year":"2022","journal-title":"Curr Opin Immunol"},{"key":"2026041320320308200_bib57","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1093\/intimm\/dxm071","article-title":"Mouse leukocyte-associated Ig-like receptor-1 (mLAIR-1) functions as an inhibitory collagen-binding receptor on immune cells","volume":"19","author":"Lebbink","year":"2007","journal-title":"Int Immunol"},{"key":"2026041320320308200_bib58","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1084\/jem.20052554","article-title":"Collagens are functional, high affinity ligands for the inhibitory immune receptor LAIR-1","volume":"203","author":"Lebbink","year":"2006","journal-title":"J Exp Med"},{"key":"2026041320320308200_bib59","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1002\/eji.200636678","article-title":"Regulated expression of the inhibitory receptor LAIR-1 on human peripheral T cells during T cell activation and differentiation","volume":"37","author":"Jansen","year":"2007","journal-title":"Eur J Immunol"},{"key":"2026041320320308200_bib60","doi-asserted-by":"crossref","first-page":"eabk3327","DOI":"10.1126\/sciadv.abk3327","article-title":"Extracellular matrix proteins regulate NK cell function in peripheral tissues","volume":"8","author":"Bunting","year":"2022","journal-title":"Sci Adv"},{"key":"2026041320320308200_bib61","doi-asserted-by":"crossref","first-page":"16136","DOI":"10.3390\/ijms232416136","article-title":"LAIR1, an ITIM-containing receptor involved in immune disorders and in hematological neoplasms","volume":"23","author":"Van Laethem","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026041320320308200_bib62","doi-asserted-by":"crossref","first-page":"3819","DOI":"10.1038\/s41467-020-17644-0","article-title":"Immunoprophylactic and immunotherapeutic control of hormone receptor-positive breast cancer","volume":"11","author":"Buqu\u00e9","year":"2020","journal-title":"Nat Commun"},{"key":"2026041320320308200_bib63","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ccr.2009.06.018","article-title":"CD4+ T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages","volume":"16","author":"DeNardo","year":"2009","journal-title":"Cancer Cell"},{"key":"2026041320320308200_bib64","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1084\/jem.20130762","article-title":"Transient regulatory T cell ablation deters oncogene-driven breast cancer and enhances radiotherapy","volume":"210","author":"Bos","year":"2013","journal-title":"J Exp Med"},{"key":"2026041320320308200_bib65","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.ccr.2012.01.008","article-title":"Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells","volume":"21","author":"Engelhardt","year":"2012","journal-title":"Cancer Cell"},{"key":"2026041320320308200_bib66","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1158\/2159-8290.CD-19-0644","article-title":"Single-cell RNA sequencing reveals stromal evolution into LRRC15+ myofibroblasts as a determinant of patient response to cancer immunotherapy","volume":"10","author":"Dominguez","year":"2020","journal-title":"Cancer Discov"},{"key":"2026041320320308200_bib67","doi-asserted-by":"crossref","first-page":"16007","DOI":"10.1117\/1.JBO.19.1.016007","article-title":"Computational segmentation of collagen fibers from second harmonic generation images of breast cancer","volume":"19","author":"Bredfeldt","year":"2014","journal-title":"J Biomed Opt"},{"key":"2026041320320308200_bib68","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1016\/j.bpj.2014.08.029","article-title":"Remodeling of fibrous extracellular matrices by contractile cells: predictions from discrete fiber network simulations","volume":"107","author":"Abhilash","year":"2014","journal-title":"Biophys J"},{"key":"2026041320320308200_bib69","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1111\/pbi.12929","article-title":"Dissecting genomic hotspots underlying seed protein, oil, and sucrose content in an interspecific mapping population of soybean using high-density linkage mapping","volume":"16","author":"Patil","year":"2018","journal-title":"Plant Biotechnol J"},{"key":"2026041320320308200_bib70","doi-asserted-by":"crossref","first-page":"e2116718119","DOI":"10.1073\/pnas.2116718119","article-title":"Glycosaminoglycans modulate long-range mechanical communication between cells in collagen networks","volume":"119","author":"Chen","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026041320320308200_bib71","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"2026041320320308200_bib72","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/s13059-019-1874-1","article-title":"Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression","volume":"20","author":"Hafemeister","year":"2019","journal-title":"Genome Biol"},{"key":"2026041320320308200_bib73","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s13059-015-0844-5","article-title":"MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data","volume":"16","author":"Finak","year":"2015","journal-title":"Genome Biol"},{"key":"2026041320320308200_bib74","doi-asserted-by":"crossref","first-page":"10.9.1","DOI":"10.1002\/cpcb.2","article-title":"Preparation of extracellular matrices produced by cultured and primary fibroblasts","volume":"71","author":"Franco-Barraza","year":"2016","journal-title":"Curr Protoc Cell Biol"}],"container-title":["Cancer Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-23-0426\/3448032\/cd-23-0426.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-23-0426\/3449274\/cd-23-0426.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/14\/7\/1302\/3470122\/cd-23-0426.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/14\/7\/1302\/3470122\/cd-23-0426.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:32:18Z","timestamp":1776126738000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article\/14\/7\/1302\/746123\/Senescent-CAFs-Mediate-Immunosuppression-and-Drive"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,29]]},"references-count":74,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4,29]]},"published-print":{"date-parts":[[2024,7,1]]}},"URL":"https:\/\/doi.org\/10.1158\/2159-8290.cd-23-0426","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1158\/2159-8290.27026318.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026315","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026303","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026315.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026309","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026312.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026306.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026291","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026303.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026309.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026297","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026300","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026300.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026312","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026306","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026318","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026288.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026294","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026321.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026291.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026288","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026297.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026321","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.27026294.v1","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1158\/2159-8290.c.7451444","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.c.7451444.v1","asserted-by":"object"}]},"ISSN":["2159-8274","2159-8290"],"issn-type":[{"value":"2159-8274","type":"print"},{"value":"2159-8290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,29]]}}}