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Adv."],"published-print":{"date-parts":[[2025,6,13]]},"abstract":"<jats:p>\n                    The impact of chemotherapy-induced tumor cell pyroptosis on fibroblasts, a key stromal cell type within the tumor microenvironment (TME), remains unexplored. Here, we report morphologically and molecularly distinct subtypes of cancer-associated fibroblasts (CAFs) in bladder cancer, including \u03b1SMA\n                    <jats:sup>+<\/jats:sup>\n                    IL-6\n                    <jats:sup>\u2212<\/jats:sup>\n                    myofibroblastic CAFs (myCAFs), \u03b1SMA\n                    <jats:sup>\u2212<\/jats:sup>\n                    IL-6\n                    <jats:sup>+<\/jats:sup>\n                    inflammatory CAFs (iCAFs), and hybrid i\/myCAFs. Caspase-1\u2013dependent tumor pyroptosis releases several inflammatory chemokines, converting \u03b1SMA\n                    <jats:sup>+<\/jats:sup>\n                    CAF into iCAFs in a CCR6-dependent manner. This is clinically relevant, as a fibroblast gene signature driven by iCAF markers and collagen type III is enriched in patients with chemoresistant bladder cancer after neoadjuvant chemotherapy. Contrary to the current notion, iCAFs, rather than myCAFs, produce collagen III in response to chemotherapy, supporting the expansion of cancer stem cells (CSCs). Thus, tumor cell pyroptosis initiates an iCAF-CSC feedforward loop that drives chemoresistance, indicating that inflammatory cell death is not universally beneficial to anticancer therapy, depending on the target cell type.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adt8697","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T13:59:04Z","timestamp":1749650344000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":19,"title":["Caspase-1\u2013dependent pyroptosis converts \u03b1SMA\n                    <sup>+<\/sup>\n                    CAFs into collagen-III\n                    <sup>high<\/sup>\n                    iCAFs to fuel chemoresistant cancer stem cells"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2992-3960","authenticated-orcid":true,"given":"Hongbo","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Urology, Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8906-6465","authenticated-orcid":true,"given":"Stephen Q. R.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Urology, Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3728-4680","authenticated-orcid":true,"given":"Ethan","family":"Subel","sequence":"additional","affiliation":[{"name":"Department of Urology, Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8200-961X","authenticated-orcid":true,"given":"Yung Hsing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology, Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3580-0924","authenticated-orcid":true,"given":"Yu-Cheng","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, Taipei Medical University, Taipei City, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0325-3719","authenticated-orcid":true,"given":"Kazukuni","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University, Stanford, CA 94305, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8984-2233","authenticated-orcid":true,"given":"Mark Ellie","family":"Alonzo","sequence":"additional","affiliation":[{"name":"Department of Urology, Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX 77030, USA."},{"name":"Graduate Program in Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Karabicici","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7610-7291","authenticated-orcid":true,"given":"Xen Ping","family":"Hoi","sequence":"additional","affiliation":[{"name":"Department of Urology, Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX 77030, USA."},{"name":"Graduate Program in Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armine","family":"Kasabyan","sequence":"additional","affiliation":[{"name":"Department of Urology, Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX 77030, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianxing","family":"Mo","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics, H. 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