{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:37:38Z","timestamp":1777019858198,"version":"3.51.4"},"posted":{"date-parts":[[2026,4,20]]},"group-title":"Cancer Biology","reference-count":61,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["EB029122"],"award-info":[{"award-number":["EB029122"]}]},{"name":"NIH","award":["GM140929"],"award-info":[{"award-number":["GM140929"]}]},{"name":"NIH","award":["CA262815"],"award-info":[{"award-number":["CA262815"]}]},{"name":"NIH","award":["P30CA014089"],"award-info":[{"award-number":["P30CA014089"]}]},{"name":"Private"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Cancer-associated fibroblasts (CAFs) contribute to immune exclusion and therapy resistance in solid tumors, limiting the efficacy of chimeric antigen receptor (CAR) T cell and immune cell therapy. To overcome this, we developed a transcription factor (TF)-based strategy to reprogram prostate-derived CAFs (pCAFs) into normal fibroblast-like cells (NFs). We prioritized TFs enriched in quiescent stellate cells\u2014Vitamin D receptor (VDR), Peroxisome Proliferator-Activated Receptor gamma (PPAR\u03b3), and p53\u2014and selected VDR for proof-of-concept studies. Lentiviral VDR expression in pCAFs produced VDR-reprogrammed NFs (VDR-rpNFs) with reduced CAF markers, increased ATP, and suppressed TGF-\u03b2 and IL6, indicating phenotypic and metabolic reversion. In both\n                  <jats:italic>in vitro<\/jats:italic>\n                  3D co-cultures and\n                  <jats:italic>in vivo<\/jats:italic>\n                  , VDR-rpNFs disrupted tumor architecture, enhanced CAR T cell infiltration, and reduced necrosis. PPAR\u03b3- and p53-rpNFs showed similar reprogramming effects. These results suggest TF-guided fibroblast reprogramming as a viable strategy to remodel the tumor microenvironment and improve CAR T cell efficacy in solid tumors.\n                <\/jats:p>","DOI":"10.64898\/2026.04.15.718753","type":"posted-content","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T06:35:17Z","timestamp":1776753317000},"source":"Crossref","is-referenced-by-count":0,"title":["Transcription Factor\u2013Mediated Reprogramming of Cancer-Associated Fibroblasts Reveals Targetable Vulnerabilities in Solid Tumors"],"prefix":"10.64898","author":[{"given":"Nan Sook","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Aerospace and Mechanical Engineering;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyankan","family":"Datta","sequence":"additional","affiliation":[{"name":"Department of Aerospace and Mechanical Engineering;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Alfred E. 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