{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T11:47:10Z","timestamp":1792928830748,"version":"4.5.0"},"reference-count":246,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002382","name":"King Faisal Specialist Hospital and Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002382","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    T cell fitness has emerged as a critical determinant of the efficacy and persistence of Chimeric Antigen Receptor (CAR)-T cell therapy. Defined by the capacity of T cells to proliferate, resist exhaustion, persist\n                    <jats:italic>in vivo<\/jats:italic>\n                    , and exert sustained effector functions, T cell fitness reflects the integration of a dynamic network of intrinsic and extrinsic regulatory mechanisms. In this review, we present a comprehensive synthesis of the molecular and cellular foundations underlying T cell fitness, emphasizing the influence of differentiation trajectories, signaling pathways, metabolic reprogramming, and epigenetic modifications. We further discuss the impact of patient-specific conditions such as age as well as disease biology, prior therapeutic exposures, and timing and quality of T cell collection, on the phenotypic and functional efficacy of CAR-T cell products. Beyond delineating these determinants, we highlight emerging strategies aimed at enhancing T cell fitness. Importantly, we propose T cell fitness as an integrated, multi-layered systems property emerging from the interaction between differentiation state, signaling architecture, metabolic\u2013mitochondrial competence, epigenetic stability, and host-specific inflammatory and treatment-related pressures. We introduce a mechanistic framework that links these layers across the CAR-T therapeutic timeline from leukapheresis to post-infusion tumor engagement and outline how this framework can be operationalized into measurable parameters to guide patient stratification, manufacturing decisions, and rational therapeutic interventions.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1762453","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:56:32Z","timestamp":1771397792000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Mechanistic basis and therapeutic modulation of T cell fitness to enhance CAR-T cell efficacy in hematological malignancies"],"prefix":"10.3389","volume":"17","author":[{"given":"Karama","family":"Makni-Maalej","sequence":"first","affiliation":[{"name":"Translational Cancer Research Facility, National Center for Cancer Care and Research, Hamad Medical Corporation","place":["Doha, Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaykhah Mujahhiz","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Stem Cell Transplantation & Cellular Therapy, King Faisal Specialist Hospital and Research Centre","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Queenie","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Translational Cancer Research Facility, National Center for Cancer Care and Research, Hamad Medical Corporation","place":["Doha, Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Osman","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Hematology, Stem Cell Transplantation & Cellular Therapy, King Faisal Specialist Hospital and Research Centre","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarra","family":"Mestiri","sequence":"additional","affiliation":[{"name":"Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation","place":["Doha, Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salim","family":"Bougarn","sequence":"additional","affiliation":[{"name":"Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation","place":["Doha, Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waad","family":"Amir","sequence":"additional","affiliation":[{"name":"Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation","place":["Doha, Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed","family":"Farhatullah","sequence":"additional","affiliation":[{"name":"Department of Hematology, Stem Cell Transplantation & Cellular Therapy, King Faisal Specialist Hospital and Research Centre","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Kharfan-Dabaja","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program","place":["Jacksonville, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maysaloun","family":"Merhi","sequence":"additional","affiliation":[{"name":"Translational Cancer Research Facility, National Center for Cancer Care and Research, Hamad Medical Corporation","place":["Doha, Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riad El","family":"Fakih","sequence":"additional","affiliation":[{"name":"Department of Hematology, Stem Cell Transplantation & Cellular Therapy, King Faisal Specialist Hospital and Research Centre","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Aljurf","sequence":"additional","affiliation":[{"name":"Department of Hematology, Stem Cell Transplantation & Cellular Therapy, King Faisal Specialist Hospital and Research Centre","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Dermime","sequence":"additional","affiliation":[{"name":"Translational Cancer Research Facility, National Center for Cancer Care and Research, Hamad Medical Corporation","place":["Doha, Qatar"]},{"name":"College of Health Sciences, Qatar University","place":["Doha, Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1188049","article-title":"From bench to bedside: the history and progress of CAR T cell therapy","volume":"14","author":"Mitra","year":"2023","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12943-023-01723-z","article-title":"CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances","volume":"22","author":"Maalej","year":"2023","journal-title":"Mol Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e21776","article-title":"CAR-T cell therapy for hematological Malignancies: History, status and promise","volume":"9","author":"Wang","year":"2023","journal-title":"Heliyon"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.948125","article-title":"A review of CAR T cells and adoptive T-cell therapies in lymphoid and solid organ Malignancies","volume":"31","author":"Parums","year":"2025","journal-title":"Med Sci Monit"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1159\/000543806","article-title":"Multi-targeting CAR-T cell strategies to overcome immune evasion in lymphoid and myeloid Malignancies","volume":"48","author":"Peter","year":"2025","journal-title":"Oncol Res Treat"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2378543","DOI":"10.1080\/21645515.2024.2378543","article-title":"Approved CAR-T therapies have reproducible efficacy and safety in clinical practice","volume":"20","author":"Goyco Vera","year":"2024","journal-title":"Hum Vaccin Immunother"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.01.021","article-title":"Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells","volume":"44","author":"Kawalekar","year":"2016","journal-title":"Immunity"},{"key":"B8","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41408-021-00459-7","article-title":"CAR-T cell therapy: current limitations and potential strategies","volume":"11","author":"Sterner","year":"2021","journal-title":"Blood Cancer J"},{"key":"B9","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nrd4597","article-title":"The pharmacology of second-generation chimeric antigen receptors","volume":"14","author":"van der Stegen","year":"2015","journal-title":"Nat Rev Drug Discov"},{"key":"B10","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s13643-021-01588-7","article-title":"Efficacy and safety of CD22 chimeric antigen receptor (CAR) T cell therapy in patients with B cell Malignancies: a protocol for a systematic review and meta-analysis","volume":"10","author":"Adeel","year":"2021","journal-title":"Syst Rev"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/BS9.0000000000000173","article-title":"CAR-T cell therapy: Where are we now, and where are we heading","volume":"5","author":"Wang","year":"2023","journal-title":"Blood Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"878209","DOI":"10.3389\/fimmu.2022.878209","article-title":"CAR-T cell performance: how to improve their persistence","volume":"13","author":"Lopez-Cantillo","year":"2022","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0306-5","article-title":"A guide to cancer immunotherapy: from T cell basic science to clinical practice","volume":"20","author":"Waldman","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.780442","article-title":"T cell fitness and autologous CAR T cell therapy in haematologic Malignancy","volume":"12","author":"Mehta","year":"2021","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.02.007","article-title":"T cell metabolic fitness in antitumor immunity","volume":"36","author":"Siska","year":"2015","journal-title":"Trends Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002555","article-title":"Understanding T cell phenotype for the design of effective chimeric antigen receptor T cell therapies","volume":"9","author":"Tantalo","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B17","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/s41392-023-01471-y","article-title":"T cells in health and disease","volume":"8","author":"Sun","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/cancers8030036","article-title":"Different subsets of T cells, memory, effector functions, and CAR-T immunotherapy","volume":"8","author":"Golubovskaya","year":"2016","journal-title":"Cancers (Basel)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001278","article-title":"CD45RA distinguishes CD4+CD25+CD127-\/low TSDR demethylated regulatory T cell subpopulations with differential stability and susceptibility to tacrolimus-mediated inhibition of suppression","volume":"101","author":"Arroyo Hornero","year":"2017","journal-title":"Transplantation"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e20","DOI":"10.4110\/in.2020.20.e20","article-title":"The roles of CCR7 for the homing of memory CD8+ T cells into their survival niches","volume":"20","author":"Choi","year":"2020","journal-title":"Immune Netw"},{"key":"B21","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.jcyt.2017.03.067","article-title":"Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion","volume":"19","author":"Kaartinen","year":"2017","journal-title":"Cytotherapy"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-018-2155-7","article-title":"Induction of a central memory and stem cell memory phenotype in functionally active CD4(+) and CD8(+) CAR T cells produced in an automated good manufacturing practice system for the treatment of CD19(+) acute lymphoblastic leukemia","volume":"67","author":"Blaeschke","year":"2018","journal-title":"Cancer Immunol Immunother"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/cei\/uxab038","article-title":"Reference range of naive T and T memory lymphocyte subsets in peripheral blood of healthy adult","volume":"207","author":"Xia","year":"2022","journal-title":"Clin Exp Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12254","article-title":"Chimeric antigen receptor T cell persistence and memory cell formation","volume":"97","author":"McLellan","year":"2019","journal-title":"Immunol Cell Biol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/25785826.2019.1698261","article-title":"Memory T cell, exhaustion, and tumor immunity","volume":"43","author":"Ando","year":"2020","journal-title":"Immunol Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00539-6","article-title":"Cellular networks controlling T cell persistence in adoptive cell therapy","volume":"21","author":"Chan","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"100989","DOI":"10.1016\/j.isci.2020.100989","article-title":"Homeostatic cytokines drive epigenetic reprogramming of activated T cells into a \u201cNaive-memory\u201d Phenotype","volume":"23","author":"Frumento","year":"2020","journal-title":"iScience"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3483","article-title":"Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses","volume":"17","author":"Pulko","year":"2016","journal-title":"Nat Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/s41568-023-00560-y","article-title":"Dynamics and specificities of T cells in cancer immunotherapy","volume":"23","author":"Oliveira","year":"2023","journal-title":"Nat Rev Cancer"},{"key":"B30","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/leu.2015.247","article-title":"Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo","volume":"30","author":"Sommermeyer","year":"2016","journal-title":"Leukemia"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000036","article-title":"Adoptive therapy with chimeric antigen receptor-modified T cells of defined subset composition","volume":"20","author":"Riddell","year":"2014","journal-title":"Cancer J"},{"key":"B32","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.smim.2016.02.001","article-title":"Role of memory T cell subsets for adoptive immunotherapy","volume":"28","author":"Busch","year":"2016","journal-title":"Semin Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2020.12.004","article-title":"A metabolic switch to memory CAR T cells: Implications for cancer treatment","volume":"500","author":"Rostamian","year":"2021","journal-title":"Cancer Lett"},{"key":"B34","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/nm.4241","article-title":"T memory stem cells in health and disease","volume":"23","author":"Gattinoni","year":"2017","journal-title":"Nat Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.947648","article-title":"Cytokines as an important player in the context of CAR-T cell therapy for cancer: Their role in tumor immunomodulation, manufacture, and clinical implications","volume":"13","author":"Silveira","year":"2022","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-18-0466","article-title":"IL15 enhances CAR-T cell antitumor activity by reducing mTORC1 activity and preserving their stem cell memory phenotype","volume":"7","author":"Alizadeh","year":"2019","journal-title":"Cancer Immunol Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-431718","article-title":"IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors","volume":"121","author":"Cieri","year":"2013","journal-title":"Blood"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13648","article-title":"Generation and application of human induced-stem cell memory T cells for adoptive immunotherapy","volume":"109","author":"Kondo","year":"2018","journal-title":"Cancer Sci"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0000000000000229","article-title":"Adoptive transfer of interleukin-21-stimulated human CD8+ T memory stem cells efficiently inhibits tumor growth","volume":"41","author":"Chen","year":"2018","journal-title":"J Immunother"},{"key":"B40","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.immuni.2011.09.017","article-title":"An interleukin-21-interleukin-10-STAT3 pathway is critical for functional maturation of memory CD8+ T cells","volume":"35","author":"Cui","year":"2011","journal-title":"Immunity"},{"key":"B41","doi-asserted-by":"publisher","first-page":"3258","DOI":"10.1038\/s41467-024-47057-2","article-title":"Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment","volume":"15","author":"Keller","year":"2024","journal-title":"Nat Commun"},{"key":"B42","doi-asserted-by":"publisher","first-page":"3258","DOI":"10.1038\/s41467-024-47057-2","article-title":"Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open-label phase II interventional trial of pediatric patients with risk factor assessment","volume":"15","author":"Keller","year":"2024","journal-title":"Nature Communications"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1527648","article-title":"Alloreactive-free CAR-VST therapy: a step forward in long-term tumor control in viral context","volume":"15","author":"Wang","year":"2024","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/s41392-021-00823-w","article-title":"T cell receptor (TCR) signaling in health and disease","volume":"6","author":"Shah","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00624","article-title":"Regulation of T helper cell fate by TCR signal strength","volume":"11","author":"Bhattacharyya","year":"2020","journal-title":"Front Immunol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"107134","DOI":"10.1016\/j.jbc.2024.107134","article-title":"Cellular and molecular signaling towards T cell immunological self-tolerance","volume":"300","author":"Carbone","year":"2024","journal-title":"J Biol Chem"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00006","article-title":"TCR signal strength alters T-DC activation and interaction times and directs the outcome of differentiation","volume":"7","author":"van Panhuys","year":"2016","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.8.3825","article-title":"The potency of TCR signaling differentially regulates NFATc\/p activity and early IL-4 transcription in naive CD4+ T cells","volume":"168","author":"Brogdon","year":"2002","journal-title":"J Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.5.1591","article-title":"Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells","volume":"182","author":"Constant","year":"1995","journal-title":"J Exp Med"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e1006318","DOI":"10.1371\/journal.ppat.1006318","article-title":"TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection","volume":"13","author":"Maru","year":"2017","journal-title":"PloS Pathog"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/nature07657","article-title":"Complete but curtailed T-cell response to very low-affinity antigen","volume":"458","author":"Zehn","year":"2009","journal-title":"Nature"},{"key":"B52","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1097\/TP.0000000000000169","article-title":"Co-inhibitory pathways and their importance in immune regulation","volume":"98","author":"Murakami","year":"2014","journal-title":"Transplantation"},{"key":"B53","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1111\/imm.12809","article-title":"Selected signalling proteins recruited to the T-cell receptor-CD3 complex","volume":"153","author":"Ngoenkam","year":"2018","journal-title":"Immunology"},{"key":"B54","doi-asserted-by":"publisher","first-page":"a002279","DOI":"10.1101\/cshperspect.a002279","article-title":"ZAP-70: an essential kinase in T-cell signaling","volume":"2","author":"Wang","year":"2010","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"109280","DOI":"10.1016\/j.celrep.2021.109280","article-title":"Positive feedback between the T cell kinase Zap70 and its substrate LAT acts as a clustering-dependent signaling switch","volume":"35","author":"Dine","year":"2021","journal-title":"Cell Rep"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000002","article-title":"T cells and costimulation in cancer","volume":"19","author":"Maj","year":"2013","journal-title":"Cancer J"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.02.008","article-title":"Overcoming T cell exhaustion in infection and cancer","volume":"36","author":"Pauken","year":"2015","journal-title":"Trends Immunol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.162","article-title":"T-cell exhaustion in the tumor microenvironment","volume":"6","author":"Jiang","year":"2015","journal-title":"Cell Death Dis"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192461099","article-title":"Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade","volume":"99","author":"Iwai","year":"2002","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B60","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s13045-017-0486-z","article-title":"Blimp-1 impairs T cell function via upregulation of TIGIT and PD-1 in patients with acute myeloid leukemia","volume":"10","author":"Zhu","year":"2017","journal-title":"J Hematol Oncol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1038\/s41467-019-08871-1","article-title":"Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT","volume":"10","author":"Noviello","year":"2019","journal-title":"Nat Commun"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3003","article-title":"Characterization of immune dysfunction and identification of prognostic immune-related risk factors in acute myeloid leukemia","volume":"26","author":"Tang","year":"2020","journal-title":"Clin Cancer Res"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0793-1","article-title":"Leukemia-induced dysfunctional TIM-3(+)CD4(+) bone marrow T cells increase risk of relapse in pediatric B-precursor ALL patients","volume":"34","author":"Blaeschke","year":"2020","journal-title":"Leukemia"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-457531","article-title":"T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production","volume":"121","author":"Riches","year":"2013","journal-title":"Blood"},{"key":"B65","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1158\/2326-6066.CIR-15-0055","article-title":"T-cell exhaustion in multiple myeloma relapse after autotransplant: optimal timing of immunotherapy","volume":"4","author":"Chung","year":"2016","journal-title":"Cancer Immunol Res"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0270","article-title":"Primary T cells from cutaneous T-cell lymphoma skin explants display an exhausted immune checkpoint profile","volume":"6","author":"Querfeld","year":"2018","journal-title":"Cancer Immunol Res"},{"key":"B67","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s13045-016-0345-3","article-title":"T cells in multiple myeloma display features of exhaustion and senescence at the tumor site","volume":"9","author":"Zelle-Rieser","year":"2016","journal-title":"J Hematol Oncol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12943-018-0814-0","article-title":"Engineering chimeric antigen receptor-T cells for cancer treatment","volume":"17","author":"Ye","year":"2018","journal-title":"Mol Cancer"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0010-1","article-title":"Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia","volume":"24","author":"Fraietta","year":"2018","journal-title":"Nat Med"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-08-665547","article-title":"Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy","volume":"127","author":"Gardner","year":"2016","journal-title":"Blood"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-1020","article-title":"Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy","volume":"5","author":"Sotillo","year":"2015","journal-title":"Cancer Discov"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-019-2118-z","article-title":"CAR T cell therapy for hematological Malignancies","volume":"39","author":"Yang","year":"2019","journal-title":"Curr Med Sci"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0184-6","article-title":"Mechanisms of resistance to CAR T cell therapy","volume":"16","author":"Shah","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.5RU0817-315R","article-title":"Acute lymphoblastic leukemia relapse after CD19-targeted chimeric antigen receptor T cell therapy","volume":"102","author":"Wang","year":"2017","journal-title":"J Leukoc Biol"},{"key":"B75","doi-asserted-by":"publisher","first-page":"6616391","DOI":"10.1155\/2021\/6616391","article-title":"T cell exhaustion and CAR-T immunotherapy in hematological Malignancies","volume":"2021","author":"Tang","year":"2021","journal-title":"BioMed Res Int"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0146-4_17","article-title":"Analysis of CAR-mediated tonic signaling","volume":"2086","author":"Calderon","year":"2020","journal-title":"Methods Mol Biol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1165870","article-title":"Failure of ALL recognition by CAR T cells: a review of CD 19-negative relapses after anti-CD 19 CAR-T treatment in B-ALL","volume":"14","author":"Aparicio-Perez","year":"2023","journal-title":"Front Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021010930","article-title":"CD19 target evasion as a mechanism of relapse in large B-cell lymphoma treated with axicabtagene ciloleucel","volume":"138","author":"Plaks","year":"2021","journal-title":"Blood"},{"key":"B79","doi-asserted-by":"publisher","first-page":"101459","DOI":"10.1016\/j.tranon.2022.101459","article-title":"Resistance against anti-CD19 and anti-BCMA CAR T cells: Recent advances and coping strategies","volume":"22","author":"Atilla","year":"2022","journal-title":"Transl Oncol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"5570","DOI":"10.1038\/s41467-022-31818-y","article-title":"High-throughput mutagenesis identifies mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance","volume":"13","author":"Cortes-Lopez","year":"2022","journal-title":"Nat Commun"},{"key":"B81","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1186\/s12943-023-01886-9","article-title":"Safety and efficacy of a novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19 with fast on- and off-rates against non-Hodgkin lymphoma: a first-in-human study","volume":"22","author":"Zhang","year":"2023","journal-title":"Mol Cancer"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52337","article-title":"A dynamic interaction between CD19 and the tetraspanin CD81 controls B cell co-receptor trafficking","volume":"9","author":"Susa","year":"2020","journal-title":"Elife"},{"key":"B83","doi-asserted-by":"publisher","first-page":"3800","DOI":"10.1038\/s41467-025-58868-2","article-title":"IKAROS levels are associated with antigen escape in CD19- and CD22-targeted therapies for B-cell Malignancies","volume":"16","author":"Domizi","year":"2025","journal-title":"Nat Commun"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyaf150","article-title":"Commentary: is trogocytosis relevant for chimeric antigen receptor-T cells","volume":"30","author":"Toolabi","year":"2025","journal-title":"Oncologist"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1097\/BS9.0000000000000220","article-title":"A shadow in the treatment of acute leukemia: lineage switch","volume":"7","author":"Zhou","year":"2025","journal-title":"Blood Sci"},{"key":"B86","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1111\/ijlh.13923","article-title":"To B- or not to B-: A review of lineage switched acute leukemia","author":"Kurzer","year":"2022","journal-title":"Int J Lab Hematol"},{"key":"B87","doi-asserted-by":"publisher","first-page":"5845167","DOI":"10.1155\/jimr\/5845167","article-title":"Advancements and future directions of dual-target chimeric antigen receptor T-cell therapy in preclinical and clinical studies","volume":"2025","author":"Zhang","year":"2025","journal-title":"J Immunol Res"},{"key":"B88","doi-asserted-by":"publisher","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"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba1786","article-title":"Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling","volume":"372","author":"Weber","year":"2021","journal-title":"Science"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.06.004","article-title":"Ligand-induced degradation of a CAR permits reversible remote control of CAR T cell activity in vitro and in vivo","volume":"28","author":"Richman","year":"2020","journal-title":"Mol Ther"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-208795","article-title":"CD123-CAR T Cells Manufactured in the Presence of Dasatinib Induce High Grade CRS and\/or IEC-HS without Improving Efficacy in Pediatric Patients with Recurrent\/Refractory Leukemia","volume":"144","author":"Naik","year":"2024","journal-title":"Blood"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1151632","article-title":"Exhausted T cells hijacking the cancer-immunity cycle: Assets and liabilities","volume":"14","author":"Brunell","year":"2023","journal-title":"Front Immunol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-2627","article-title":"Multifactorial T-cell hypofunction that is reversible can limit the efficacy of chimeric antigen receptor-transduced human T cells in solid tumors","volume":"20","author":"Moon","year":"2014","journal-title":"Clin Cancer Res"},{"key":"B94","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s13045-019-0746-1","article-title":"Immune checkpoint blockade and CAR-T cell therapy in hematologic Malignancies","volume":"12","author":"Wang","year":"2019","journal-title":"J Hematol Oncol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-1300","article-title":"Multiplex genome editing to generate universal CAR T cells resistant to PD1 inhibition","volume":"23","author":"Ren","year":"2017","journal-title":"Clin Cancer Res"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9114","article-title":"Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model","volume":"7","author":"Suarez","year":"2016","journal-title":"Oncotarget"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4195","article-title":"Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo","volume":"36","author":"Rafiq","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15218","article-title":"A versatile system for rapid multiplex genome-edited CAR T cell generation","volume":"8","author":"Ren","year":"2017","journal-title":"Oncotarget"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1172\/JCI83092","article-title":"Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition","volume":"126","author":"Cherkassky","year":"2016","journal-title":"J Clin Invest"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13678","article-title":"The siRNA-mediated downregulation of PD-1 alone or simultaneously with CTLA-4 shows enhanced in vitro CAR-T-cell functionality for further clinical development towards the potential use in immunotherapy of melanoma","volume":"27","author":"Simon","year":"2018","journal-title":"Exp Dermatol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1038\/s41598-017-00462-8","article-title":"CRISPR\/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells","volume":"7","author":"Rupp","year":"2017","journal-title":"Sci Rep"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-018-2281-2","article-title":"CRISPR\/Cas9-mediated PD-1 disruption enhances human mesothelin-targeted CAR T cell effector functions","volume":"68","author":"Hu","year":"2019","journal-title":"Cancer Immunol Immunother"},{"key":"B103","doi-asserted-by":"publisher","first-page":"111339","DOI":"10.1016\/j.biopha.2021.111339","article-title":"ShRNA-mediated silencing of PD-1 augments the efficacy of chimeric antigen receptor T cells on subcutaneous prostate and leukemia xenograft","volume":"137","author":"Zhou","year":"2021","journal-title":"BioMed Pharmacother"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14061580","article-title":"Addressing the elephant in the immunotherapy room: effector T-cell priming versus depletion of regulatory T-cells by anti-CTLA-4 therapy","volume":"14","author":"Hong","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1315283","article-title":"TIM-3, LAG-3, or 2B4 gene disruptions increase the anti-tumor response of engineered T cells","volume":"15","author":"Cianciotti","year":"2024","journal-title":"Front Immunol"},{"key":"B106","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12943-024-02208-3","article-title":"Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy","volume":"24","author":"He","year":"2025","journal-title":"Mol Cancer"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131916","article-title":"PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation","volume":"211","author":"Noman","year":"2014","journal-title":"J Exp Med"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.08.020","article-title":"Emerging role of natural products in cancer immunotherapy","volume":"12","author":"Dong","year":"2022","journal-title":"Acta Pharm Sin B"},{"key":"B109","doi-asserted-by":"publisher","first-page":"2035117","DOI":"10.1080\/21645515.2022.2035117","article-title":"Regulatory T cells (Tregs) and their therapeutic potential against autoimmune disorders - Advances and challenges","volume":"18","author":"Goswami","year":"2022","journal-title":"Hum Vaccin Immunother"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.7150\/thno.105276","article-title":"Metabolic regulation of myeloid-derived suppressor cells in tumor immune microenvironment: targets and therapeutic strategies","volume":"15","author":"Wang","year":"2025","journal-title":"Theranostics"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3286","article-title":"Inhibition of p300 impairs Foxp3(+) T regulatory cell function and promotes antitumor immunity","volume":"19","author":"Liu","year":"2013","journal-title":"Nat Med"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0230","article-title":"Reduction of MDSCs with all-trans retinoic acid improves CAR therapy efficacy for sarcomas","volume":"4","author":"Long","year":"2016","journal-title":"Cancer Immunol Res"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.08.025","article-title":"MDSC targeting with Gemtuzumab ozogamicin restores T cell immunity and immunotherapy against cancers","volume":"47","author":"Fultang","year":"2019","journal-title":"EBioMedicine"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0346-9","article-title":"Adaptive plasticity of IL-10(+) and IL-35(+) T(reg) cells cooperatively promotes tumor T cell exhaustion","volume":"20","author":"Sawant","year":"2019","journal-title":"Nat Immunol"},{"key":"B115","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.3389\/fimmu.2017.01773","article-title":"The CXCR4-STAT3-IL-10 pathway controls the immunoregulatory function of chronic lymphocytic leukemia and is modulated by lenalidomide","volume":"8","author":"Shaim","year":"2017","journal-title":"Front Immunol"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.133977","article-title":"TGF-beta inhibition via CRISPR promotes the long-term efficacy of CAR T cells against solid tumors","volume":"5","author":"Tang","year":"2020","journal-title":"JCI Insight"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2024.04.004","article-title":"Decoding and overcoming T cell exhaustion: Epigenetic and transcriptional dynamics in CAR-T cells against solid tumors","volume":"32","author":"Ahn","year":"2024","journal-title":"Mol Ther"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1905675116","article-title":"TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8(+) T cell exhaustion","volume":"116","author":"Seo","year":"2019","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B119","doi-asserted-by":"publisher","first-page":"103941","DOI":"10.1016\/j.ebiom.2022.103941","article-title":"Improving CAR-T immunotherapy: Overcoming the challenges of T cell exhaustion","volume":"77","author":"Gumber","year":"2022","journal-title":"EBioMedicine"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-008665","article-title":"NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumors","volume":"12","author":"Nakagawara","year":"2024","journal-title":"J Immunother Cancer"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0985-x","article-title":"NR4A transcription factors limit CAR T cell function in solid tumours","volume":"567","author":"Chen","year":"2019","journal-title":"Nature"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba7365","article-title":"CRISPR-engineered T cells in patients with refractory cancer","volume":"367","author":"Stadtmauer","year":"2020","journal-title":"Science"},{"key":"B123","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41392-024-01986-y","article-title":"MEK inhibition prevents CAR-T cell exhaustion and differentiation via downregulation of c-Fos and JunB","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1324-y","article-title":"TOX is a critical regulator of tumour-specific T cell differentiation","volume":"571","author":"Scott","year":"2019","journal-title":"Nature"},{"key":"B125","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.ccell.2020.08.001","article-title":"Hematopoietic progenitor kinase1 (HPK1) mediates T cell dysfunction and is a druggable target for T cell-based immunotherapies","volume":"38","author":"Si","year":"2020","journal-title":"Cancer Cell"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00964-8","article-title":"BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells","volume":"22","author":"Seo","year":"2021","journal-title":"Nat Immunol"},{"key":"B127","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.immuni.2020.04.014","article-title":"Developmental relationships of four exhausted CD8(+) T cell subsets reveals underlying transcriptional and epigenetic landscape control mechanisms","volume":"52","author":"Beltra","year":"2020","journal-title":"Immunity"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202002566R","article-title":"Role of TCF-1 in differentiation, exhaustion, and memory of CD8(+) T cells: A review","volume":"35","author":"Zhang","year":"2021","journal-title":"FASEB J"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009309","article-title":"Regnase-1 suppresses TCF-1+ precursor exhausted T-cell formation to limit CAR-T-cell responses against ALL","volume":"138","author":"Zheng","year":"2021","journal-title":"Blood"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2025-108","article-title":"BACH2 regulates T cell lineage states to overcome dysfunction driven by tonic CAR signaling","volume":"146","author":"Chang","year":"2025","journal-title":"Blood"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02391-5","article-title":"BACH2 regulates T cell lineage state to enhance CAR T cell function","volume":"576","author":"Chang","year":"2026","journal-title":"Nat Immunol"},{"key":"B132","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41586-019-1805-z","article-title":"c-Jun overexpression in CAR T cells induces exhaustion resistance","volume":"576","author":"Lynn","year":"2019","journal-title":"Nature"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151159","article-title":"T cell metabolism drives immunity","volume":"212","author":"Buck","year":"2015","journal-title":"J Exp Med"},{"key":"B134","doi-asserted-by":"publisher","first-page":"35","DOI":"10.2147\/BTT.S365490","article-title":"Targeting metabolic reprogramming of T-cells for enhanced anti-tumor response","volume":"16","author":"Dabi","year":"2022","journal-title":"Biologics"},{"key":"B135","doi-asserted-by":"publisher","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":"B136","doi-asserted-by":"publisher","first-page":"102487","DOI":"10.1016\/j.coi.2024.102487","article-title":"Metabolic footprint and logic through the T cell life cycle","volume":"91","author":"Fan","year":"2024","journal-title":"Curr Opin Immunol"},{"key":"B137","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.it.2014.12.005","article-title":"Fatty acid metabolism in the regulation of T cell function","volume":"36","author":"Lochner","year":"2015","journal-title":"Trends Immunol"},{"key":"B138","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s40169-016-0110-9","article-title":"Clinical significance of T cell metabolic reprogramming in cancer","volume":"5","author":"Herbel","year":"2016","journal-title":"Clin Transl Med"},{"key":"B139","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/s41590-019-0589-5","article-title":"CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors","volume":"21","author":"Wang","year":"2020","journal-title":"Nat Immunol"},{"key":"B140","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1186\/s12943-023-01893-w","article-title":"Exploiting autophagy balance in T and NK cells as a new strategy to implement adoptive cell therapies","volume":"22","author":"Giansanti","year":"2023","journal-title":"Mol Cancer"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201545955","article-title":"Key roles of autophagy in regulating T-cell function","volume":"46","author":"Botbol","year":"2016","journal-title":"Eur J Immunol"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00530-z","article-title":"A comparison of chimeric antigen receptors containing CD28 versus 4-1BB costimulatory domains","volume":"18","author":"Cappell","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180397","article-title":"Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome","volume":"215","author":"Yu","year":"2018","journal-title":"J Exp Med"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2023.01.002","article-title":"Metabolism and epigenetics at the heart of T cell function","volume":"44","author":"Soriano-Baguet","year":"2023","journal-title":"Trends Immunol"},{"key":"B145","doi-asserted-by":"publisher","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":"B146","doi-asserted-by":"publisher","first-page":"165845","DOI":"10.1016\/j.bbadis.2020.165845","article-title":"Mitochondrial function in immune cells in health and disease","volume":"1866","author":"Faas","year":"2020","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2017.10.006","article-title":"Mitochondrial activity in T cells","volume":"41","author":"Desdin-Mico","year":"2018","journal-title":"Mitochondrion"},{"key":"B148","doi-asserted-by":"publisher","first-page":"6858","DOI":"10.1038\/s41467-023-42634-3","article-title":"Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1alpha-mediated glycolytic reprogramming","volume":"14","author":"Wu","year":"2023","journal-title":"Nat Commun"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2017.11.008","article-title":"Mitochondrial quality control: The role of mitophagy in aging","volume":"28","author":"Shi","year":"2018","journal-title":"Trends Cardiovasc Med"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-21-0110","article-title":"Mitochondria as playmakers of CAR T-cell fate and longevity","volume":"9","author":"Rostamian","year":"2021","journal-title":"Cancer Immunol Res"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13061229","article-title":"Metabolic and mitochondrial functioning in chimeric antigen receptor (CAR)-T cells","volume":"13","author":"Rad","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B152","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1182\/blood.2018885863","article-title":"Chronic lymphocytic leukemia cells impair mitochondrial fitness in CD8(+) T cells and impede CAR T-cell efficacy","volume":"134","author":"van Bruggen","year":"2019","journal-title":"Blood"},{"key":"B153","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41423-019-0344-8","article-title":"Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment","volume":"17","author":"Zhao","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B154","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s40164-024-00535-1","article-title":"Fueling CARs: metabolic strategies to enhance CAR T-cell therapy","volume":"13","author":"Van der Vreken","year":"2024","journal-title":"Exp Hematol Oncol"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07242-1","article-title":"FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy","volume":"629","author":"Chan","year":"2024","journal-title":"Nature"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171068","article-title":"4-1BB costimulation induces T cell mitochondrial function and biogenesis enabling cancer immunotherapeutic responses","volume":"215","author":"Menk","year":"2018","journal-title":"J Exp Med"},{"key":"B157","doi-asserted-by":"publisher","first-page":"12506","DOI":"10.1038\/s41598-022-16616-2","article-title":"Transgenic expression of IL-7 regulates CAR-T cell metabolism and enhances in vivo persistence against tumor cells","volume":"12","author":"Li","year":"2022","journal-title":"Sci Rep"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.07.018","article-title":"IL-15 preconditioning augments CAR T cell responses to checkpoint blockade for improved treatment of solid tumors","volume":"28","author":"Giuffrida","year":"2020","journal-title":"Mol Ther"},{"key":"B159","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-02060-8","article-title":"IL-10-expressing CAR T cells resist dysfunction and mediate durable clearance of solid tumors and metastases","volume":"42","author":"Zhao","year":"2024","journal-title":"Nat Biotechnol"},{"key":"B160","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaz6314","article-title":"Reprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy","volume":"13","author":"Liu","year":"2021","journal-title":"Sci Transl Med"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-3443","article-title":"Neuroblastoma arginase activity creates an immunosuppressive microenvironment that impairs autologous and engineered immunity","volume":"75","author":"Mussai","year":"2015","journal-title":"Cancer Res"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004500","article-title":"Metabolic engineering against the arginine microenvironment enhances CAR-T cell proliferation and therapeutic activity","volume":"136","author":"Fultang","year":"2020","journal-title":"Blood"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1186383","article-title":"Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy","volume":"14","author":"Li","year":"2023","journal-title":"Front Immunol"},{"key":"B164","doi-asserted-by":"publisher","first-page":"216223","DOI":"10.1016\/j.canlet.2023.216223","article-title":"Mitochondrial immune regulation and anti-tumor immunotherapy strategies targeting mitochondria","volume":"564","author":"Bai","year":"2023","journal-title":"Cancer Lett"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0365-3","article-title":"Enforced PGC-1alpha expression promotes CD8 T cell fitness, memory formation and antitumor immunity","volume":"18","author":"Dumauthioz","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B166","doi-asserted-by":"publisher","DOI":"10.2174\/1568009622666220330194149","article-title":"Peroxisome proliferator-activated receptor gamma coactivator-1 alpha: A double-edged sword in prostate cancer","volume":"22","author":"Zheng","year":"2022","journal-title":"Curr Cancer Drug Targets"},{"key":"B167","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1016\/j.celrep.2019.03.066","article-title":"Pulsatile MEK inhibition improves anti-tumor immunity and T cell function in murine kras mutant lung cancer","volume":"27","author":"Choi","year":"2019","journal-title":"Cell Rep"},{"key":"B168","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201948455","article-title":"Ex vivo blockade of PI3K gamma or delta signaling enhances the antitumor potency of adoptively transferred CD8(+) T cells","volume":"50","author":"Dwyer","year":"2020","journal-title":"Eur J Immunol"},{"key":"B169","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017011254","article-title":"Improving T-cell expansion and function for adoptive T-cell therapy using ex vivo treatment with PI3Kdelta inhibitors and VIP antagonists","volume":"2","author":"Petersen","year":"2018","journal-title":"Blood Adv"},{"key":"B170","doi-asserted-by":"publisher","first-page":"6692","DOI":"10.1038\/ncomms7692","article-title":"PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation","volume":"6","author":"Patsoukis","year":"2015","journal-title":"Nat Commun"},{"key":"B171","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.cmet.2022.03.013","article-title":"The mitochondrial pyruvate carrier regulates memory T cell differentiation and antitumor function","volume":"34","author":"Wenes","year":"2022","journal-title":"Cell Metab"},{"key":"B172","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s00262-018-2243-8","article-title":"beta-Adrenergic signaling blocks murine CD8(+) T-cell metabolic reprogramming during activation: a mechanism for immunosuppression by adrenergic stress","volume":"68","author":"Qiao","year":"2019","journal-title":"Cancer Immunol Immunother"},{"key":"B173","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.cmet.2023.12.010","article-title":"Mitochondrial isocitrate dehydrogenase impedes CAR T cell function by restraining antioxidant metabolism and histone acetylation","volume":"36","author":"Si","year":"2024","journal-title":"Cell Metab"},{"key":"B174","doi-asserted-by":"publisher","DOI":"10.1101\/2024.02.26.582129","article-title":"Dissecting the role of CAR signaling architectures on T cell activation and persistence using pooled screening and single-cell sequencing","author":"Castellanos-Rueda","year":"2024","journal-title":"bioRxiv"},{"key":"B175","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1335424","article-title":"Recent advances on CAR-T signaling pave the way for prolonged persistence and new modalities in clinic","volume":"15","author":"Smirnov","year":"2024","journal-title":"Front Immunol"},{"key":"B176","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010208","article-title":"Integrating binding affinity and tonic signaling enables a rational CAR design for augmented T cell function","volume":"12","author":"Barden","year":"2024","journal-title":"J Immunother Cancer"},{"key":"B177","doi-asserted-by":"publisher","first-page":"115973","DOI":"10.1016\/j.celrep.2025.115973","article-title":"CAR-T cells containing CD28 versus 4-1BB co-stimulatory domains show distinct metabolic profiles in patients","volume":"44","author":"Cook","year":"2025","journal-title":"Cell Rep"},{"key":"B178","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-20-0451","article-title":"Modifications to the framework regions eliminate chimeric antigen receptor tonic signaling","volume":"9","author":"Landoni","year":"2021","journal-title":"Cancer Immunol Res"},{"key":"B179","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0110-7","article-title":"Calcium signalling in T cells","volume":"19","author":"Trebak","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"B180","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1698442","article-title":"Engineering the next generation of CAR T- cells: precision modifications, logic gates and universal strategies to overcome exhaustion and tumor resistance","volume":"15","author":"Garcia-Robledo","year":"2026","journal-title":"Front Oncol"},{"key":"B181","doi-asserted-by":"publisher","first-page":"122390","DOI":"10.1016\/j.lfs.2023.122390","article-title":"Chronic inflammation and cancer; the two sides of a coin","volume":"338","author":"Fernandes","year":"2024","journal-title":"Life Sci"},{"key":"B182","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.979116","article-title":"Tumor accomplice: T cell exhaustion induced by chronic inflammation","volume":"13","author":"Fang","year":"2022","journal-title":"Front Immunol"},{"key":"B183","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1061-7","article-title":"Characteristics of anti-CD19 CAR T cell infusion products associated with efficacy and toxicity in patients with large B cell lymphomas","volume":"26","author":"Deng","year":"2020","journal-title":"Nat Med"},{"key":"B184","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.042523","article-title":"What does tumour necrosis factor excess do to the immune system long term","author":"Clark","year":"2005","journal-title":"Ann Rheum Dis"},{"key":"B185","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1038\/s41591-021-01248-2","article-title":"Author Correction: Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia","volume":"27","author":"Fraietta","year":"2021","journal-title":"Nat Med"},{"key":"B186","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01618","article-title":"The changing landscape of naive T cell receptor repertoire with human aging","volume":"9","author":"Egorov","year":"2018","journal-title":"Front Immunol"},{"key":"B187","doi-asserted-by":"publisher","DOI":"10.4161\/hv.24696","article-title":"The effect of ageing of the immune system on vaccination responses","volume":"9","author":"Lord","year":"2013","journal-title":"Hum Vaccin Immunother"},{"key":"B188","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxaa006","article-title":"Physiology and pathology of T-cell aging","volume":"32","author":"Minato","year":"2020","journal-title":"Int Immunol"},{"key":"B189","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2022.840827","article-title":"Inflammation, immune senescence, and dysregulated immune regulation in the elderly","volume":"3","author":"Shive","year":"2022","journal-title":"Front Aging"},{"key":"B190","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41423-021-00756-y","article-title":"Regulation of antitumor immunity by inflammation-induced epigenetic alterations","volume":"19","author":"Karin","year":"2022","journal-title":"Cell Mol Immunol"},{"key":"B191","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s12948-017-0077-0","article-title":"Immunosenescence in aging: between immune cells depletion and cytokines up-regulation","volume":"15","author":"Ventura","year":"2017","journal-title":"Clin Mol Allergy"},{"key":"B192","doi-asserted-by":"publisher","first-page":"101840","DOI":"10.1016\/j.smim.2023.101840","article-title":"Beyond youth: Understanding CAR T cell fitness in the context of immunological aging","volume":"70","author":"Noll","year":"2023","journal-title":"Semin Immunol"},{"key":"B193","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1091","article-title":"The clock is ticking: the impact of ageing on T cell metabolism","volume":"8","author":"Quinn","year":"2019","journal-title":"Clin Transl Immunol"},{"key":"B194","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00121","article-title":"T cell aging: a review of the transcriptional changes determined from genome-wide analysis","volume":"4","author":"Chen","year":"2013","journal-title":"Front Immunol"},{"key":"B195","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/s41408-024-01193-6","article-title":"Impact of T cell characteristics on CAR-T cell therapy in hematological Malignancies","volume":"14","author":"Tao","year":"2024","journal-title":"Blood Cancer J"},{"key":"B196","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2024.11.013","article-title":"Efficient manufacturing of CAR-T cells from whole blood: a scalable approach to reduce costs and enhance accessibility in cancer therapy","volume":"27","author":"Traynor","year":"2024","journal-title":"Cytotherapy"},{"key":"B197","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1101495","article-title":"CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies","volume":"14","author":"Zhang","year":"2023","journal-title":"Front Immunol"},{"key":"B198","doi-asserted-by":"publisher","DOI":"10.1172\/JCI150807","article-title":"CAR T cell manufacturing from naive\/stem memory T lymphocytes enhances antitumor responses while curtailing cytokine release syndrome","volume":"132","author":"Arcangeli","year":"2022","journal-title":"J Clin Invest"},{"key":"B199","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s13045-023-01504-7","article-title":"Reprogramming T cell differentiation and exhaustion in CAR-T cell therapy","volume":"16","author":"Bulliard","year":"2023","journal-title":"J Hematol Oncol"},{"key":"B200","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.cmet.2022.11.005","article-title":"Age-associated remodeling of T cell immunity and metabolism","volume":"35","author":"Han","year":"2023","journal-title":"Cell Metab"},{"key":"B201","doi-asserted-by":"publisher","DOI":"10.1159\/000354194","article-title":"Impact of interleukin-6 in hematological Malignancies","volume":"40","author":"Burger","year":"2013","journal-title":"Transfus Med Hemother"},{"key":"B202","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-246660","article-title":"Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma","volume":"115","author":"Prabhala","year":"2010","journal-title":"Blood"},{"key":"B203","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02153","article-title":"Conventional treatment for multiple myeloma drives premature aging phenotypes and metabolic dysfunction in T cells","volume":"11","author":"Cooke","year":"2020","journal-title":"Front Immunol"},{"key":"B204","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0873-2","article-title":"T-cells in chronic lymphocytic leukemia: Guardians or drivers of disease","volume":"34","author":"Roessner","year":"2020","journal-title":"Leukemia"},{"key":"B205","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-679134","article-title":"Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia","volume":"127","author":"Fraietta","year":"2016","journal-title":"Blood"},{"key":"B206","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-1239-y","article-title":"Alterations of T-cell-mediated immunity in acute myeloid leukemia","volume":"39","author":"Li","year":"2020","journal-title":"Oncogene"},{"key":"B207","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.120974","article-title":"Signatures of CD8+ T cell dysfunction in AML patients and their reversibility with response to chemotherapy","volume":"3","author":"Knaus","year":"2018","journal-title":"JCI Insight"},{"key":"B208","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.03.052","article-title":"CAR-T cell therapy for treatment of acute myeloid leukemia, advances and outcomes","volume":"33","author":"Khalifeh","year":"2025","journal-title":"Mol Ther"},{"key":"B209","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e39731","article-title":"Immunoediting in acute myeloid leukemia: Reappraising T cell exhaustion and the aberrant antigen processing machinery in leukemogenesis","volume":"10","author":"Wang","year":"2024","journal-title":"Heliyon"},{"key":"B210","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/s41408-018-0069-4","article-title":"Bone marrow CD8 T cells express high frequency of PD-1 and exhibit reduced anti-leukemia response in newly diagnosed AML patients","volume":"8","author":"Jia","year":"2018","journal-title":"Blood Cancer J"},{"key":"B211","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s13045-020-00853-x","article-title":"Expression patterns of immune checkpoints in acute myeloid leukemia","volume":"13","author":"Chen","year":"2020","journal-title":"J Hematol Oncol"},{"key":"B212","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.MA0119-021R","article-title":"A skewed distribution and increased PD-1+Vbeta+CD4+\/CD8+ T cells in patients with acute myeloid leukemia","volume":"106","author":"Huang","year":"2019","journal-title":"J Leukoc Biol"},{"key":"B213","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41392-025-02269-w","article-title":"CAR-T cell therapy for cancer: current challenges and future directions","volume":"10","author":"Zugasti","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B214","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-024-06117-9","article-title":"Immunosuppressive microenvironment in acute myeloid leukemia: overview, therapeutic targets and corresponding strategies","volume":"103","author":"Zha","year":"2024","journal-title":"Ann Hematol"},{"key":"B215","doi-asserted-by":"publisher","DOI":"10.3390\/cancers18010107","article-title":"Is there a future for CAR-T therapy in acute myeloid leukemia","volume":"18","author":"Alati","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B216","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s40164-025-00726-4","article-title":"Emerging strategies in CAR-T cell therapy for acute myeloid leukemia: overcoming heterogeneity and improving safety through dual-antigen targeting","volume":"14","author":"Ocana-Cara","year":"2025","journal-title":"Exp Hematol Oncol"},{"key":"B217","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.5MR0520-466R","article-title":"Impact of age-, cancer-, and treatment-driven inflammation on T cell function and immunotherapy","volume":"108","author":"Quinn","year":"2020","journal-title":"J Leukoc Biol"},{"key":"B218","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.2.754.014k39_754_762","article-title":"Prolonged CD4 depletion after sequential autologous peripheral blood progenitor cell infusions in children and young adults","volume":"96","author":"Mackall","year":"2000","journal-title":"Blood"},{"key":"B219","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.9.3789","article-title":"Constraints on CD4 recovery postchemotherapy in adults: thymic insufficiency and apoptotic decline of expanded peripheral CD4 cells","volume":"90","author":"Hakim","year":"1997","journal-title":"Blood"},{"key":"B220","doi-asserted-by":"publisher","first-page":"320ra3","DOI":"10.1126\/scitranslmed.aad5222","article-title":"Early memory phenotypes drive T cell proliferation in patients with pediatric Malignancies","volume":"8","author":"Singh","year":"2016","journal-title":"Sci Transl Med"},{"key":"B221","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1314","article-title":"Naive T-cell Deficits at Diagnosis and after Chemotherapy Impair Cell Therapy Potential in Pediatric Cancers","volume":"9","author":"Das","year":"2019","journal-title":"Cancer Discov"},{"key":"B222","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01797","article-title":"Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: results from the US lymphoma CAR T consortium","volume":"41","author":"Wang","year":"2023","journal-title":"J Clin Oncol"},{"key":"B223","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01097","article-title":"Recent bendamustine treatment before apheresis has a negative impact on outcomes in patients with large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy","volume":"42","author":"Iacoboni","year":"2024","journal-title":"J Clin Oncol"},{"key":"B224","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18831","article-title":"Risk factors for CAR-T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan","volume":"202","author":"Jo","year":"2023","journal-title":"Br J Haematol"},{"key":"B225","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02496-0","article-title":"Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial","volume":"29","author":"Lin","year":"2023","journal-title":"Nat Med"},{"key":"B226","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/s41408-023-00886-8","article-title":"Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy","volume":"13","author":"Ferreri","year":"2023","journal-title":"Blood Cancer J"},{"key":"B227","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015526","article-title":"Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents","volume":"141","author":"Cohen","year":"2023","journal-title":"Blood"},{"key":"B228","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022015956","article-title":"T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals","volume":"140","author":"Philipp","year":"2022","journal-title":"Blood"},{"key":"B229","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01405","article-title":"Blinatumomab nonresponse and high-disease burden are associated with inferior outcomes after CD19-CAR for B-ALL","volume":"40","author":"Myers","year":"2022","journal-title":"J Clin Oncol"},{"key":"B230","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01281-7","article-title":"Determinants of CD19-positive vs CD19-negative relapse after tisagenlecleucel for B-cell acute lymphoblastic leukemia","volume":"35","author":"Dourthe","year":"2021","journal-title":"Leukemia"},{"key":"B231","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000692","article-title":"CAR T-cell therapy is effective for CD19-dim B-lymphoblastic leukemia but is impacted by prior blinatumomab therapy","volume":"3","author":"Pillai","year":"2019","journal-title":"Blood Adv"},{"key":"B232","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002587","article-title":"CD19 antibody-drug conjugate therapy in DLBCL does not preclude subsequent responses to CD19-directed CAR T-cell therapy","volume":"4","author":"Thapa","year":"2020","journal-title":"Blood Adv"},{"key":"B233","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2021.1986219","article-title":"CD19 expression is maintained in DLBCL patients after treatment with tafasitamab plus lenalidomide in the L-MIND study","volume":"63","author":"Duell","year":"2022","journal-title":"Leuk Lymphoma"},{"key":"B234","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007923","article-title":"Sequencing T-cell redirection therapies leads to deep and durable responses in patients with relapsed\/refractory myeloma","volume":"7","author":"Mouhieddine","year":"2023","journal-title":"Blood Adv"},{"key":"B235","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.122627","article-title":"Safety and tolerability of conditioning chemotherapy followed by CD19-targeted CAR T cells for relapsed\/refractory CLL","volume":"5","author":"Geyer","year":"2019","journal-title":"JCI Insight"},{"key":"B236","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019002936","article-title":"Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure","volume":"135","author":"Gauthier","year":"2020","journal-title":"Blood"},{"key":"B237","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-007803","article-title":"CD8(+) chimeric antigen receptor T cells manufactured in absence of CD4(+) cells exhibit hypofunctional phenotype","volume":"11","author":"Lee","year":"2023","journal-title":"J Immunother Cancer"},{"key":"B238","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023021306","article-title":"CAR T cells and time-limited ibrutinib as treatment for relapsed\/refractory mantle cell lymphoma: the phase 2 TARMAC study","volume":"143","author":"Minson","year":"2024","journal-title":"Blood"},{"key":"B239","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01739-2","article-title":"Outcomes of first therapy after CD19-CAR-T treatment failure in large B-cell lymphoma","volume":"37","author":"Alarcon Tomas","year":"2023","journal-title":"Leukemia"},{"key":"B240","doi-asserted-by":"publisher","DOI":"10.1158\/2643-3230.BCD-22-0074","article-title":"Anti-BCMA\/CD19 CAR T cells with early immunomodulatory maintenance for multiple myeloma responding to initial or later-line therapy","volume":"4","author":"Garfall","year":"2023","journal-title":"Blood Cancer Discov"},{"key":"B241","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.19751","article-title":"Chimeric antigen receptor T-cell therapy for haematological Malignancies: Insights from fundamental and translational research to bedside practice","volume":"205","author":"Gregoire","year":"2024","journal-title":"Br J Haematol"},{"key":"B242","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/bjh.18816","article-title":"Early lymphocyte collection for anti-CD19 CART production improves T-cell fitness in patients with relapsed\/refractory diffuse large B-cell lymphoma","volume":"202","author":"Dubnikov Sharon","year":"2023","journal-title":"Br J Haematol"},{"key":"B243","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2019000600","article-title":"T-cell phenotypes associated with effective CAR T-cell therapy in postinduction vs relapsed multiple myeloma","volume":"3","author":"Garfall","year":"2019","journal-title":"Blood Adv"},{"key":"B244","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25951","article-title":"Commercial anti-CD19 CAR T cell therapy for patients with relapsed\/refractory aggressive B cell lymphoma in a European center","volume":"95","author":"Sesques","year":"2020","journal-title":"Am J Hematol"},{"key":"B245","doi-asserted-by":"publisher","DOI":"10.1172\/JCI126397","article-title":"B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma","volume":"129","author":"Cohen","year":"2019","journal-title":"J Clin Invest"},{"key":"B246","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010709","article-title":"Prior chemotherapy deteriorates T-cell quality for CAR T-cell therapy in B-cell non-Hodgkin's lymphoma","volume":"13","author":"Junkuhn","year":"2025","journal-title":"J Immunother Cancer"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1762453\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:32:33Z","timestamp":1771932753000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1762453\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":246,"alternative-id":["10.3389\/fimmu.2026.1762453"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1762453","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]},"article-number":"1762453"}}