{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T09:34:25Z","timestamp":1763544865353,"version":"3.38.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>TLR agonists are effective at treating superficial cancerous lesions, but their use internally for other types of tumors remains challenging because of toxicity. In this article, we report that murine and human naive CD4+ T cells that sequester Pam3Cys4 (CD4+ TPam3) become primed for Th1 differentiation. CD4+ TPam3 cells encoding the OVA-specific TCR OT2, when transferred into mice bearing established TGF-\u03b2\u2013OVA\u2013expressing thymomas, produce high amounts of IFN-\u03b3 and sensitize tumors to PD-1\/programmed cell death ligand 1 blockade\u2013induced rejection. In contrast, naive OT2 cells without Pam3Cys4 cargo are prone to TGF-\u03b2\u2013dependent inducible regulatory Foxp3+ CD4+ T cell conversion and accelerate tumor growth that is largely unaffected by PD-1\/programmed cell death ligand 1 blockade. Ex vivo analysis reveals that CD4+ TPam3 cells are resistant to TGF-\u03b2\u2013mediated gene expression through Akt activation controlled by inputs from the TCR and a TLR2-MyD88\u2013dependent PI3K signaling pathway. These data show that CD4+ TPam3 cells are capable of Th1 differentiation in the presence of TGF-\u03b2, suggesting a novel approach to adoptive cell therapy.<\/jats:p>","DOI":"10.4049\/jimmunol.1700396","type":"journal-article","created":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T18:15:22Z","timestamp":1512584122000},"page":"847-856","source":"Crossref","is-referenced-by-count":9,"title":["Naive CD4+ T Cells Carrying a TLR2 Agonist Overcome TGF-\u03b2\u2013Mediated Tumor Immune Evasion"],"prefix":"10.1093","volume":"200","author":[{"given":"Mohsen","family":"Ibrahim","sequence":"first","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine , St. Louis, MO 63108"},{"name":"Department of Medical-Surgical Science and Translational Medicine, Sapienza University of Rome , 00189 Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Scozzi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine , St. Louis, MO 63108"},{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome , 00189 Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelsey A","family":"Toth","sequence":"additional","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine , St. Louis, MO 63108"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4764-6223","authenticated-orcid":false,"given":"Donatella","family":"Ponti","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome , 04100 Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Kreisel","sequence":"additional","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine , St. Louis, MO 63108"},{"name":"Department of Pathology and Immunology, Washington University School of Medicine , St. Louis, MO 63108"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Menna","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Science and Translational Medicine, Sapienza University of Rome , 00189 Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5220-0587","authenticated-orcid":false,"given":"Elena","family":"De Falco","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome , 04100 Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"D\u2019Andrilli","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Science and Translational Medicine, Sapienza University of Rome , 00189 Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erino A","family":"Rendina","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Science and Translational Medicine, Sapienza University of Rome , 00189 Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Calogero","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome , 04100 Rome,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander S","family":"Krupnick","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Virginia School of Medicine , Charlottesville, VA 22098"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew E","family":"Gelman","sequence":"additional","affiliation":[{"name":"Department of Surgery, Washington University School of Medicine , St. Louis, MO 63108"},{"name":"Department of Medical-Surgical Science and Translational Medicine, Sapienza University of Rome , 00189 Rome,","place":["Italy"]},{"name":"Department of Pathology and Immunology, Washington University School of Medicine , St. Louis, MO 63108"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,1,15]]},"reference":[{"key":"2025030610011116400_r1","doi-asserted-by":"crossref","first-page":"949","DOI":"10.2217\/imt.09.70","article-title":"Toll-like receptor agonists in cancer therapy","volume":"1","author":"Adams","year":"2009","journal-title":"Immunotherapy"},{"key":"2025030610011116400_r2","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1111\/j.1365-2133.2005.06486.x","article-title":"Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe","volume":"152","author":"Schulze","year":"2005","journal-title":"Br. 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