{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:24:51Z","timestamp":1790573091325,"version":"4.1.0"},"reference-count":42,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":370,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001368","name":"V Foundation for Cancer Research","doi-asserted-by":"publisher","award":["T2021-015"],"award-info":[{"award-number":["T2021-015"]}],"id":[{"id":"10.13039\/100001368","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006939","name":"Emory University","doi-asserted-by":"publisher","award":["2P30 CA138292-09"],"award-info":[{"award-number":["2P30 CA138292-09"]}],"id":[{"id":"10.13039\/100006939","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006942","name":"Medical University of South Carolina","doi-asserted-by":"publisher","award":["P30 CA138313"],"award-info":[{"award-number":["P30 CA138313"]}],"id":[{"id":"10.13039\/100006942","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA175061"],"award-info":[{"award-number":["R01 CA175061"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA208514"],"award-info":[{"award-number":["R01 CA208514"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA228406"],"award-info":[{"award-number":["R01 CA228406"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21 CA266088"],"award-info":[{"award-number":["R21 CA266088"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R50 CA233168"],"award-info":[{"award-number":["R50 CA233168"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011621","name":"Winship Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2023,7]]},"DOI":"10.1016\/j.ymthe.2023.04.010","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T07:04:36Z","timestamp":1681974276000},"page":"2120-2131","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":18,"title":["Augmenting TCR signal strength and ICOS costimulation results in metabolically fit and therapeutically potent human CAR Th17 cells"],"prefix":"10.1016","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1316-260X","authenticated-orcid":false,"given":"Megan M.","family":"Wyatt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan W.","family":"Huff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle H.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian R.","family":"Neal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Medvec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo O.","family":"Rangel Rivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubrey S.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia M.","family":"Rivera Reyes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah M.","family":"Knochelmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Riley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory B.","family":"Lesinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrystal M.","family":"Paulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2023.04.010_bib1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nrc2355","article-title":"Adoptive cell transfer: a clinical path to effective cancer immunotherapy","volume":"8","author":"Rosenberg","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ymthe.2023.04.010_bib2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nri3191","article-title":"Adoptive immunotherapy for cancer: harnessing the T\u00a0cell response","volume":"12","author":"Restifo","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ymthe.2023.04.010_bib3","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1126\/science.aar6711","article-title":"CAR T\u00a0cell immunotherapy for human cancer","volume":"359","author":"June","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2023.04.010_bib4","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.3389\/fimmu.2018.01740","article-title":"CAR T\u00a0cells in solid tumors: blueprints for building effective therapies","volume":"9","author":"Knochelmann","year":"2018","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ymthe.2023.04.010_bib5","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/nm.1882","article-title":"Virus-specific T\u00a0cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma","volume":"14","author":"Pule","year":"2008","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2023.04.010_bib6","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s40425-017-0230-9","article-title":"Current approaches to increase CAR T\u00a0cell potency in solid tumors: targeting the tumor microenvironment","volume":"5","author":"Scarf\u00f2","year":"2017","journal-title":"J.\u00a0Immunother. Cancer"},{"key":"10.1016\/j.ymthe.2023.04.010_bib7","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1007\/s00262-017-2034-7","article-title":"The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T\u00a0cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity","volume":"66","author":"Thistlethwaite","year":"2017","journal-title":"Cancer Immunol. Immunother."},{"key":"10.1016\/j.ymthe.2023.04.010_bib8","doi-asserted-by":"crossref","first-page":"5921","DOI":"10.4049\/jimmunol.159.12.5921","article-title":"Effects of CD28 costimulation on long-term proliferation of CD4+ T\u00a0cells in the absence of exogenous feeder cells","volume":"159","author":"Levine","year":"1997","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.ymthe.2023.04.010_bib9","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1006\/clim.2002.5277","article-title":"A cell-based artificial antigen-presenting cell coated with anti-CD3 and CD28 antibodies enables rapid expansion and long-term growth of CD4\u00a0T lymphocytes","volume":"105","author":"Thomas","year":"2002","journal-title":"Clin. Immunol."},{"key":"10.1016\/j.ymthe.2023.04.010_bib10","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1600-065X.2008.00628.x","article-title":"Th17 cells in human disease","volume":"223","author":"Tesmer","year":"2008","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.ymthe.2023.04.010_bib11","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1146\/annurev.immunol.021908.132710","article-title":"IL-17 and Th17 cells","volume":"27","author":"Korn","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.ymthe.2023.04.010_bib12","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1182\/blood-2007-11-120998","article-title":"Tumor-specific Th17-polarized cells eradicate large established melanoma","volume":"112","author":"Muranski","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2023.04.010_bib13","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/j.immuni.2011.09.019","article-title":"Th17 cells are long lived and retain a stem cell-like molecular signature","volume":"35","author":"Muranski","year":"2011","journal-title":"Immunity"},{"key":"10.1016\/j.ymthe.2023.04.010_bib14","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.90772","article-title":"Th17 cells are refractory to senescence and retain robust antitumor activity after long-term ex\u00a0vivo expansion","volume":"2","author":"Bowers","year":"2017","journal-title":"JCI Insight"},{"key":"10.1016\/j.ymthe.2023.04.010_bib15","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3389\/fimmu.2014.00276","article-title":"Th17 cells in cancer: the ultimate identity crisis","volume":"5","author":"Bailey","year":"2014","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ymthe.2023.04.010_bib16","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00262-016-1797-6","article-title":"Exploiting IL-17-producing CD4+ and CD8+ T\u00a0cells to improve cancer immunotherapy in the clinic","volume":"65","author":"Majchrzak","year":"2016","journal-title":"Cancer Immunol. Immunother."},{"key":"10.1016\/j.ymthe.2023.04.010_bib17","doi-asserted-by":"crossref","first-page":"104ra100","DOI":"10.1126\/scitranslmed.3002949","article-title":"Human TH17 cells are long-lived effector memory cells","volume":"3","author":"Kryczek","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2023.04.010_bib18","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/nm.2446","article-title":"A human memory T\u00a0cell subset with stem cell\u2013like properties","volume":"17","author":"Gattinoni","year":"2011","journal-title":"Nat. Med."},{"key":"10.1016\/j.ymthe.2023.04.010_bib19","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s12967-016-0973-y","article-title":"A short CD3\/CD28 costimulation combined with IL-21 enhance the generation of human memory stem T\u00a0cells for adoptive immunotherapy","volume":"14","author":"Alvarez-Fern\u00e1ndez","year":"2016","journal-title":"J.\u00a0Transl. Med."},{"key":"10.1016\/j.ymthe.2023.04.010_bib20","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.intimp.2012.10.023","article-title":"Impact of polyclonal anti-CD3\/CD28-coated magnetic bead expansion methods on T\u00a0cell proliferation, differentiation and function","volume":"15","author":"Shi","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ymthe.2023.04.010_bib21","doi-asserted-by":"crossref","first-page":"4829","DOI":"10.1182\/blood-2010-03-272153","article-title":"Low-strength T-cell activation promotes Th17 responses","volume":"116","author":"Purvis","year":"2010","journal-title":"Blood"},{"key":"10.1016\/j.ymthe.2023.04.010_bib22","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aba7443","article-title":"Identification of human CD4+ T\u00a0cell populations with distinct antitumor activity","volume":"6","author":"Nelson","year":"2020","journal-title":"Sci. Adv."},{"key":"10.1016\/j.ymthe.2023.04.010_bib23","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/16717","article-title":"ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28","volume":"397","author":"Hutloff","year":"1999","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2023.04.010_bib24","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nature08097","article-title":"Enhancing CD8 T-cell memory by modulating fatty acid metabolism","volume":"460","author":"Pearce","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.ymthe.2023.04.010_bib25","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.immuni.2011.12.007","article-title":"Mitochondrial respiratory capacity is a critical regulator of CD8+ T\u00a0cell memory development","volume":"36","author":"van der Windt","year":"2012","journal-title":"Immunity"},{"key":"10.1016\/j.ymthe.2023.04.010_bib26","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1084\/jem.20151159","article-title":"T cell metabolism drives immunity","volume":"212","author":"Buck","year":"2015","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.ymthe.2023.04.010_bib27","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cell.2016.05.035","article-title":"Mitochondrial dynamics controls T\u00a0cell fate through metabolic programming","volume":"166","author":"Buck","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2023.04.010_bib28","doi-asserted-by":"crossref","first-page":"4479","DOI":"10.1172\/JCI69589","article-title":"Inhibiting glycolytic metabolism enhances CD8+ T\u00a0cell memory and antitumor function","volume":"123","author":"Sukumar","year":"2013","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.ymthe.2023.04.010_bib29","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cmet.2015.11.002","article-title":"Mitochondrial membrane potential identifies cells with enhanced stemness for cellular therapy","volume":"23","author":"Sukumar","year":"2016","journal-title":"Cell Metab."},{"key":"10.1016\/j.ymthe.2023.04.010_bib30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1743-7075-2-33","article-title":"Phosphoenolpyruvate carboxykinase and the critical role of cataplerosis in the control of hepatic metabolism","volume":"2","author":"Hakimi","year":"2005","journal-title":"Nutr. Metab."},{"key":"10.1016\/j.ymthe.2023.04.010_bib31","doi-asserted-by":"crossref","first-page":"55ra78","DOI":"10.1126\/scitranslmed.3000448","article-title":"The inducible costimulator (ICOS) is critical for the development of human T(H)17 cells","volume":"2","author":"Paulos","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2023.04.010_bib32","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.4049\/jimmunol.1401082","article-title":"The inducible costimulator augments Tc17 cell responses to self and tumor tissue","volume":"194","author":"Nelson","year":"2015","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.ymthe.2023.04.010_bib33","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0005087","article-title":"CD28 co-stimulation down regulates Th17 development","volume":"4","author":"Bouguermouh","year":"2009","journal-title":"PLoS One"},{"key":"10.1016\/j.ymthe.2023.04.010_bib34","doi-asserted-by":"crossref","first-page":"106","DOI":"10.4049\/jimmunol.1501766","article-title":"The immune-metabolic basis of effector memory CD4+ T\u00a0cell function under hypoxic conditions","volume":"196","author":"Dimeloe","year":"2016","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.ymthe.2023.04.010_bib35","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1016\/j.celrep.2020.01.022","article-title":"Mitochondrial oxidative phosphorylation regulates the fate decision between pathogenic Th17 and regulatory T\u00a0cells","volume":"30","author":"Shin","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.ymthe.2023.04.010_bib36","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/s42255-020-0219-4","article-title":"Inosine is an alternative carbon source for CD8+-T-cell function under glucose restriction","volume":"2","author":"Wang","year":"2020","journal-title":"Nat. Metab."},{"key":"10.1016\/j.ymthe.2023.04.010_bib37","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.cell.2015.08.012","article-title":"Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T\u00a0cell responses","volume":"162","author":"Ho","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2023.04.010_bib38","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41556-017-0002-2","article-title":"A Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8(+) T\u00a0cells","volume":"20","author":"Ma","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.ymthe.2023.04.010_bib39","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.cell.2016.09.031","article-title":"L-arginine modulates T\u00a0cell metabolism and enhances survival and anti-tumor activity","volume":"167","author":"Geiger","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.ymthe.2023.04.010_bib40","doi-asserted-by":"crossref","DOI":"10.1038\/mto.2016.11","article-title":"Toxicity and management in CAR T-cell therapy","volume":"3","author":"Bonifant","year":"2016","journal-title":"Mol. Ther. Oncolytics"},{"key":"10.1016\/j.ymthe.2023.04.010_bib41","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1073\/pnas.0813101106","article-title":"Control of large, established tumor xenografts with genetically retargeted human T\u00a0cells containing CD28 and CD137 domains","volume":"106","author":"Carpenito","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2023.04.010_bib42","doi-asserted-by":"crossref","first-page":"611","DOI":"10.3389\/fonc.2018.00611","article-title":"PCK1 downregulation promotes TXNRD1 expression and hepatoma cell growth via the nrf2\/keap1 pathway","volume":"8","author":"Tuo","year":"2018","journal-title":"Front. Oncol."}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001623002083?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001623002083?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T18:08:48Z","timestamp":1761502128000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001623002083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7]]},"references-count":42,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["S1525001623002083"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2023.04.010","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.10.28.514057","asserted-by":"object"}]},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2023,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Augmenting TCR signal strength and ICOS costimulation results in metabolically fit and therapeutically potent human CAR Th17 cells","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2023.04.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}]}}