{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T03:16:35Z","timestamp":1794107795619,"version":"4.8.0"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100240"],"award-info":[{"award-number":["82100240"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000182"],"award-info":[{"award-number":["82000182"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["212300410269"],"award-info":[{"award-number":["212300410269"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019092","name":"Science Fund for Distinguished Young Scholars of Hunan Province","doi-asserted-by":"publisher","award":["232300421049"],"award-info":[{"award-number":["232300421049"]}],"id":[{"id":"10.13039\/501100019092","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cytokine"],"published-print":{"date-parts":[[2024,12]]},"DOI":"10.1016\/j.cyto.2024.156758","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T19:52:31Z","timestamp":1726602751000},"page":"156758","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"special_numbering":"C","title":["Optimizing CAR-T cell Culture: Differential effects of IL-2, IL-12, and IL-21 on CAR-T cells"],"prefix":"10.1016","volume":"184","author":[{"given":"Mengmeng","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JingJing","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanxiang","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxiang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zan","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohong","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuya","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quande","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongqun","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cyto.2024.156758_b0005","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.876339","article-title":"Impact of Manufacturing Procedures on CAR T Cell Functionality","volume":"13","author":"Watanabe","year":"2022","journal-title":"Front. Immunol."},{"issue":"5","key":"10.1016\/j.cyto.2024.156758_b0010","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41422-023-00789-0","article-title":"Tuning charge density of chimeric antigen receptor optimizes tonic signaling and CAR-T cell fitness","volume":"33","author":"Chen","year":"2023","journal-title":"Cell Res."},{"issue":"1","key":"10.1016\/j.cyto.2024.156758_b0015","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40164-022-00285-y","article-title":"Generation and clinical potential of functional T lymphocytes from gene-edited pluripotent stem cells","volume":"11","author":"Guo","year":"2022","journal-title":"Exp. Hematol. Oncol."},{"key":"10.1016\/j.cyto.2024.156758_b0020","doi-asserted-by":"crossref","unstructured":"G. L\u00f3pez-Cantillo, C. Urue\u00f1a, B.A. Camacho, C. Ram\u00edrez-Segura, CAR-T Cell Performance: How to Improve Their Persistence?, 13 (2022).","DOI":"10.3389\/fimmu.2022.878209"},{"issue":"1","key":"10.1016\/j.cyto.2024.156758_b0025","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s40364-022-00434-9","article-title":"Strategies to enhance CAR-T persistence","volume":"10","author":"Liu","year":"2022","journal-title":"Biomarker Res."},{"issue":"1","key":"10.1016\/j.cyto.2024.156758_b0030","doi-asserted-by":"crossref","first-page":"4737","DOI":"10.1038\/s41467-023-40115-1","article-title":"Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting","volume":"14","author":"Lee","year":"2023","journal-title":"Nat. Commun."},{"issue":"1","key":"10.1016\/j.cyto.2024.156758_b0035","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1038\/s41467-023-37646-y","article-title":"Inducible expression of interleukin-12 augments the efficacy of affinity-tuned chimeric antigen receptors in murine solid tumor models","volume":"14","author":"Yang","year":"2023","journal-title":"Nat. Commun."},{"issue":"1","key":"10.1016\/j.cyto.2024.156758_b0040","doi-asserted-by":"crossref","first-page":"6472","DOI":"10.1038\/s41598-021-85960-6","article-title":"Metabolic changes of Interleukin-12\/15\/18-stimulated human NK cells","volume":"11","author":"Terr\u00e9n","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.cyto.2024.156758_b0045","doi-asserted-by":"crossref","unstructured":"X. Shen, P. Dong, J. Kong, N. Sun, F. Wang, L. Sang, Y. Xu, M. Zhang, X. Chen, R. Guo, S. Wang, Q. Lin, Z. Jiang, S. Xu, C. Zhang, Z. Bian, W. Wang, R. Guo, Targeted single-cell RNA sequencing analysis reveals metabolic reprogramming and the ferroptosis-resistant state in hematologic malignancies, 41(8) (2023) 1343-1356.","DOI":"10.1002\/cbf.3869"},{"issue":"Supplement 1","key":"10.1016\/j.cyto.2024.156758_b0050","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1182\/blood-2023-179444","article-title":"Ferroptosis Inhibition Generates TCF-1 + CAR-T Cells with Enhanced Persistence and Cytotoxicity","volume":"142","author":"Harada","year":"2023","journal-title":"Blood"},{"key":"10.1016\/j.cyto.2024.156758_b0055","unstructured":"R. Guo, J. Kong, P. Tang, S. Wang, L. Sang, L. Liu, R. Guo, K. Yan, M. Qi, Z. Bian, Y. Song, Z. Jiang, Y. Li, Unbiased Single-Cell Sequencing of Hematopoietic and Immune Cells from Aplastic Anemia Reveals the Contributors of Hematopoiesis Failure and Dysfunctional Immune Regulation, n\/a(n\/a) 2304539."},{"issue":"2","key":"10.1016\/j.cyto.2024.156758_b0060","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1182\/bloodadvances.2023010607","article-title":"Nonactivated and IL-7 cultured CD19-specific CAR T cells are enriched in stem cell phenotypes and functionally superior","volume":"8","author":"Wang","year":"2024","journal-title":"Blood Adv."},{"issue":"5","key":"10.1016\/j.cyto.2024.156758_b0065","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S1074-7613(00)80566-X","article-title":"Biochemical mechanisms of IL-2-regulated Fas-mediated T cell apoptosis","volume":"8","author":"Refaeli","year":"1998","journal-title":"Immunity"},{"issue":"12","key":"10.1016\/j.cyto.2024.156758_b0070","doi-asserted-by":"crossref","first-page":"6719","DOI":"10.4049\/jimmunol.0904089","article-title":"Distinct roles for IL-2 and IL-15 in the differentiation and survival of CD8+ effector and memory T cells","volume":"184","author":"Mitchell","year":"2010","journal-title":"J Immunol"},{"issue":"2","key":"10.1016\/j.cyto.2024.156758_b0075","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1016\/j.bbrc.2017.12.041","article-title":"Short-term culture with IL-2 is beneficial for potent memory chimeric antigen receptor T cell production","volume":"495","author":"Zhang","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"14","key":"10.1016\/j.cyto.2024.156758_b0080","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.3390\/cancers13143534","article-title":"IL-15 Enhances the Persistence and Function of BCMA-Targeting CAR-T Cells Compared to IL-2 or IL-15\/IL-7 by Limiting CAR-T Cell Dysfunction and Differentiation","volume":"13","author":"Battram","year":"2021","journal-title":"Cancers"},{"key":"10.1016\/j.cyto.2024.156758_b0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2023.110078","article-title":"CCL17 acts as an antitumor chemokine in micromilieu-driven immune skewing","volume":"118","author":"Li","year":"2023","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"10.1016\/j.cyto.2024.156758_b0090","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1186\/s12967-022-03566-6","article-title":"Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level","volume":"20","author":"Zhang","year":"2022","journal-title":"J. Transl. Med."},{"issue":"1","key":"10.1016\/j.cyto.2024.156758_b0095","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40364-021-00265-0","article-title":"Single-cell map of diverse immune phenotypes in the acute myeloid leukemia microenvironment","volume":"9","author":"Guo","year":"2021","journal-title":"Biomarker Res."},{"key":"10.1016\/j.cyto.2024.156758_b0100","doi-asserted-by":"crossref","DOI":"10.1038\/s41556-024-01360-8","article-title":"A guideline on the molecular ecosystem regulating ferroptosis","author":"Dai","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.cyto.2024.156758_b0105","doi-asserted-by":"crossref","DOI":"10.3389\/fmolb.2021.675179","article-title":"IL-21 Optimizes the CAR-T Cell Preparation Through Improving Lentivirus Mediated Transfection Efficiency of T Cells and Enhancing CAR-T Cell Cytotoxic Activities","volume":"8","author":"Du","year":"2021","journal-title":"Front. Mol. Biosci."},{"issue":"12","key":"10.1016\/j.cyto.2024.156758_b0110","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.jcyt.2020.08.005","article-title":"Inducible secretion of IL-21 augments anti-tumor activity of piggyBac-manufactured chimeric antigen receptor T cells","volume":"22","author":"\u0160tach","year":"2020","journal-title":"Cytotherapy"},{"issue":"9","key":"10.1016\/j.cyto.2024.156758_b0115","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1158\/2159-8290.CD-20-1677","article-title":"Integrative Bulk and Single-Cell Profiling of Premanufacture T-cell Populations Reveals Factors Mediating Long-Term Persistence of CAR T-cell Therapy","volume":"11","author":"Chen","year":"2021","journal-title":"Cancer Discov"},{"issue":"6","key":"10.1016\/j.cyto.2024.156758_b0120","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41422-019-0160-9","article-title":"Cortical branched actin determines cell cycle progression","volume":"29","author":"Molinie","year":"2019","journal-title":"Cell Res."},{"key":"10.1016\/j.cyto.2024.156758_b0125","doi-asserted-by":"crossref","unstructured":"J. Tian, L. Jiang, H. Li, J. Dan, Y. Luo, The dual role of the DREAM\/G2M pathway in non-tumorigenic immortalization of senescent cells, 14(2) (2024) 331-343.","DOI":"10.1002\/2211-5463.13748"},{"issue":"11","key":"10.1016\/j.cyto.2024.156758_b0130","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/j.ccell.2022.09.013","article-title":"Depletion of BATF in CAR-T cells enhances antitumor activity by inducing resistance against exhaustion and formation of central memory cells","volume":"40","author":"Zhang","year":"2022","journal-title":"Cancer Cell"},{"issue":"12","key":"10.1016\/j.cyto.2024.156758_b0135","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/s41571-022-00689-z","article-title":"Clinical implications of T cell exhaustion for cancer immunotherapy","volume":"19","author":"Chow","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.cyto.2024.156758_b0140","doi-asserted-by":"crossref","unstructured":"D. Hermans, S. Gautam, J.C. Garc\u00eda-Ca\u00f1averas, D. Gromer, S. Mitra, R. Spolski, P. Li, S. Christensen, R. Nguyen, J.X. Lin, J. Oh, N. Du, S. Veenbergen, J. Fioravanti, R. Ebina-Shibuya, C. Bleck, L.M. Neckers, J.D. Rabinowitz, L. Gattinoni, W.J. Leonard, Lactate dehydrogenase inhibition synergizes with IL-21 to promote CD8(+) T cell stemness and antitumor immunity, Proceedings of the National Academy of Sciences of the United States of America 117(11) (2020) 6047-6055.","DOI":"10.1073\/pnas.1920413117"},{"issue":"9","key":"10.1016\/j.cyto.2024.156758_b0145","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1038\/s41418-022-00957-6","article-title":"Ubiquitin ligase E3 HUWE1\/MULE targets transferrin receptor for degradation and suppresses ferroptosis in acute liver injury","volume":"29","author":"Wu","year":"2022","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.cyto.2024.156758_b0150","doi-asserted-by":"crossref","DOI":"10.1038\/s41590-024-01746-8","article-title":"Targeting JMJD1C to selectively disrupt tumor Treg cell fitness enhances antitumor immunity","author":"Long","year":"2024","journal-title":"Nat. Immunol."},{"issue":"17","key":"10.1016\/j.cyto.2024.156758_b0155","doi-asserted-by":"crossref","first-page":"13125","DOI":"10.18632\/oncotarget.24442","article-title":"IL-21 modulates memory and exhaustion phenotype of T-cells in a fatty acid oxidation-dependent manner","volume":"9","author":"Loschinski","year":"2018","journal-title":"Oncotarget"},{"key":"10.1016\/j.cyto.2024.156758_b0160","doi-asserted-by":"crossref","unstructured":"J. Zhang, T. He, L. Xue, H. Guo, Senescent T cells: a potential biomarker and target for cancer therapy, eBioMedicine 68 (2021).","DOI":"10.1016\/j.ebiom.2021.103409"},{"key":"10.1016\/j.cyto.2024.156758_b0165","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1146\/annurev-immunol-042617-053352","article-title":"Signaling and Function of Interleukin-2 in T Lymphocytes","volume":"36","author":"Ross","year":"2018","journal-title":"Annu. Rev. Immunol."},{"issue":"3","key":"10.1016\/j.cyto.2024.156758_b0170","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41590-020-00850-9","article-title":"IL-2 regulates tumor-reactive CD8+ T cell exhaustion by activating the aryl hydrocarbon receptor","volume":"22","author":"Liu","year":"2021","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.cyto.2024.156758_b0175","doi-asserted-by":"crossref","unstructured":"Y. Gao, S. Liu, Y. Huang, H. Wang, Y. Zhao, X. Cui, Y. Peng, F. Li, Y. Zhang, CAR T cells engineered to secrete IFN-\u03ba induce tumor ferroptosis via an IFNAR\/STAT1\/ACSL4 axis, Cancer Immunol Res (2024).","DOI":"10.1158\/2326-6066.c.7567707"},{"key":"10.1016\/j.cyto.2024.156758_b0180","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1182\/blood-2023-179444","article-title":"Ferroptosis Inhibition Generates TCF-1 + CAR-T Cells with Enhanced Persistence and Cytotoxicity","volume":"142","author":"Harada","year":"2023","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.cyto.2024.156758_b0185","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s40364-021-00264-1","article-title":"Anti-Mesothelin CAR T cell therapy for malignant mesothelioma","volume":"9","author":"Castelletti","year":"2021","journal-title":"Biomarker Res."},{"issue":"625","key":"10.1016\/j.cyto.2024.156758_b0190","doi-asserted-by":"crossref","first-page":"eabg7565","DOI":"10.1126\/scitranslmed.abg7565","article-title":"An orthogonal IL-2 and IL-2R\u03b2 system drives persistence and activation of CAR T cells and clearance of bulky lymphoma","volume":"13","author":"Aspuria","year":"2021","journal-title":"Sci Transl Med"},{"issue":"Supplement 1","key":"10.1016\/j.cyto.2024.156758_b0195","doi-asserted-by":"crossref","first-page":"4545","DOI":"10.1182\/blood-2018-99-116294","article-title":"Interleukin 21 Enhances Survival and Expansion of CAR T Cells Via Inhibition of Their Terminal Differentiation during Interaction with Tumor Target Cells","volume":"132","author":"\u0160tach","year":"2018","journal-title":"Blood"},{"issue":"9","key":"10.1016\/j.cyto.2024.156758_b0200","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1038\/s41375-023-01966-1","article-title":"Culture expansion of CAR T cells results in aberrant DNA methylation that is associated with adverse clinical outcome","volume":"37","author":"Salz","year":"2023","journal-title":"Leukemia"},{"key":"10.1016\/j.cyto.2024.156758_b0205","doi-asserted-by":"crossref","unstructured":"J. Huang, S. Jin, R. Guo, W. Wu, C. Yang, Y. Qin, Q. Chen, X. He, J. Qu, Z. Yang, Histone lysine demethylase KDM5B facilitates proliferation and suppresses apoptosis in human acute myeloid leukemia cells through the miR-140-3p\/BCL2 axis, (2024).","DOI":"10.1261\/rna.079865.123"}],"container-title":["Cytokine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S104346662400262X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S104346662400262X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T10:31:29Z","timestamp":1778581889000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S104346662400262X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":41,"alternative-id":["S104346662400262X"],"URL":"https:\/\/doi.org\/10.1016\/j.cyto.2024.156758","relation":{},"ISSN":["1043-4666"],"issn-type":[{"value":"1043-4666","type":"print"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Optimizing CAR-T cell Culture: Differential effects of IL-2, IL-12, and IL-21 on CAR-T cells","name":"articletitle","label":"Article Title"},{"value":"Cytokine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cyto.2024.156758","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"156758"}}