{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:34:55Z","timestamp":1789508095365,"version":"build-2803163510"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-19-1-0196"],"award-info":[{"award-number":["W81XWH-19-1-0196"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA046934"],"award-info":[{"award-number":["P30CA046934"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Immunol"],"published-print":{"date-parts":[[2025,1]]},"DOI":"10.1038\/s41590-024-02034-1","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T11:02:21Z","timestamp":1735815741000},"page":"68-81","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Antigen experience history directs distinct functional states of CD8+ CAR T cells during the antileukemia response"],"prefix":"10.1038","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4144-7277","authenticated-orcid":false,"given":"Kole R.","family":"DeGolier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Danis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"D\u2019Antonio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8111-8697","authenticated-orcid":false,"given":"Jennifer","family":"Cimons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4557-7255","authenticated-orcid":false,"given":"Michael","family":"Yarnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9065-7895","authenticated-orcid":false,"given":"Ross M.","family":"Kedl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1181-0418","authenticated-orcid":false,"given":"M. Eric","family":"Kohler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0546-7799","authenticated-orcid":false,"given":"James P.","family":"Scott-Browne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8044-5226","authenticated-orcid":false,"given":"Terry J.","family":"Fry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"2034_CR1","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/s41586-023-05707-3","volume":"614","author":"L Labanieh","year":"2023","unstructured":"Labanieh, L. & Mackall, C. L. CAR immune cells: design principles, resistance and the next generation. Nature 614, 635\u2013648 (2023).","journal-title":"Nature"},{"key":"2034_CR2","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/leu.2015.247","volume":"30","author":"D Sommermeyer","year":"2016","unstructured":"Sommermeyer, D. et al. Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia 30, 492\u2013500 (2016).","journal-title":"Leukemia"},{"key":"2034_CR3","doi-asserted-by":"crossref","first-page":"eaaw9414","DOI":"10.1126\/scitranslmed.aaw9414","volume":"11","author":"H Qin","year":"2019","unstructured":"Qin, H. et al. CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies. Sci. Transl. Med. 11, eaaw9414 (2019).","journal-title":"Sci. Transl. Med."},{"key":"2034_CR4","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1158\/1078-0432.CCR-22-2038","volume":"29","author":"I Aldoss","year":"2023","unstructured":"Aldoss, I. et al. Favorable activity and safety profile of memory-enriched CD19-targeted chimeric antigen receptor T-cell therapy in adults with high-risk relapsed\/refractory ALL. Clin. Cancer Res. 29, 742\u2013753 (2023).","journal-title":"Clin. Cancer Res."},{"key":"2034_CR5","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.3390\/cancers15071935","volume":"15","author":"M Alvanou","year":"2023","unstructured":"Alvanou, M. et al. Empowering the potential of CAR-T cell immunotherapies by epigenetic reprogramming. Cancers 15, 1935 (2023).","journal-title":"Cancers"},{"key":"2034_CR6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/imr.12943","volume":"300","author":"AB Frias","year":"2021","unstructured":"Frias, A. B., Boi, S. K., Lan, X. & Youngblood, B. Epigenetic regulation of T cell adaptive immunity. Immunol. Rev. 300, 9\u201321 (2021).","journal-title":"Immunol. Rev."},{"key":"2034_CR7","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","volume":"15","author":"EJ Wherry","year":"2015","unstructured":"Wherry, E. J. & Kurachi, M. Molecular and cellular insights into T cell exhaustion. Nat. Rev. Immunol. 15, 486\u2013499 (2015).","journal-title":"Nat. Rev. Immunol."},{"key":"2034_CR8","doi-asserted-by":"crossref","unstructured":"Heitzeneder, S. et al. GPC2-CAR T cells tuned for low antigen density mediate potent activity against neuroblastoma without toxicity. Cancer Cell 40, 53\u201369.e9 (2022).","DOI":"10.1016\/j.ccell.2021.12.005"},{"key":"2034_CR9","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nm.4441","volume":"24","author":"TJ Fry","year":"2018","unstructured":"Fry, T. J. et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat. Med. 24, 20\u201328 (2018).","journal-title":"Nat. Med."},{"key":"2034_CR10","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1158\/2159-8290.CD-19-0945","volume":"10","author":"RG Majzner","year":"2020","unstructured":"Majzner, R. G. et al. Tuning the antigen density requirement for CAR T-cell activity. Cancer Discov. 10, 702\u2013723 (2020).","journal-title":"Cancer Discov."},{"key":"2034_CR11","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.immuni.2011.08.010","volume":"35","author":"R Kumar","year":"2011","unstructured":"Kumar, R. et al. Increased sensitivity of antigen-experienced T cells through the enrichment of oligomeric T cell receptor complexes. Immunity 35, 375\u2013387 (2011).","journal-title":"Immunity"},{"key":"2034_CR12","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1084\/jem.20131271","volume":"211","author":"ER Mehlhop-Williams","year":"2014","unstructured":"Mehlhop-Williams, E. R. & Bevan, M. J. Memory CD8+ T cells exhibit increased antigen threshold requirements for recall proliferation. J. Exp. Med. 211, 345\u2013356 (2014).","journal-title":"J. Exp. Med."},{"key":"2034_CR13","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1182\/blood-2011-02-337360","volume":"118","author":"X Wang","year":"2011","unstructured":"Wang, X. et al. A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood 118, 1255\u20131263 (2011).","journal-title":"Blood"},{"key":"2034_CR14","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1182\/blood-2017-12-815548","volume":"132","author":"H Qin","year":"2018","unstructured":"Qin, H. et al. Murine pre-B-cell ALL induces T-cell dysfunction not fully reversed by introduction of a chimeric antigen receptor. Blood 132, 1899\u20131910 (2018).","journal-title":"Blood"},{"key":"2034_CR15","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms12320","volume":"7","author":"E Jacoby","year":"2016","unstructured":"Jacoby, E. et al. CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity. Nat. Commun. 7, 12320 (2016).","journal-title":"Nat. Commun."},{"key":"2034_CR16","doi-asserted-by":"crossref","first-page":"eaag1209","DOI":"10.1126\/scitranslmed.aag1209","volume":"9","author":"Y Yang","year":"2017","unstructured":"Yang, Y. et al. TCR engagement negatively affects CD8 but not CD4 CAR T cell expansion and leukemic clearance. Sci. Transl. Med. 9, eaag1209 (2017).","journal-title":"Sci. Transl. Med."},{"key":"2034_CR17","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.112911","volume":"42","author":"DL Ivanova","year":"2023","unstructured":"Ivanova, D. L. et al. Vaccine adjuvant-elicited CD8+ T cell immunity is co-dependent on T-bet and FOXO1. Cell Rep. 42, 112911 (2023).","journal-title":"Cell Rep."},{"key":"2034_CR18","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2021.109591","volume":"36","author":"J Klarquist","year":"2021","unstructured":"Klarquist, J. et al. B cells promote CD8 T cell primary and memory responses to subunit vaccines. Cell Rep. 36, 109591 (2021).","journal-title":"Cell Rep."},{"key":"2034_CR19","doi-asserted-by":"crossref","first-page":"eaas9822","DOI":"10.1126\/sciimmunol.aas9822","volume":"3","author":"J Klarquist","year":"2018","unstructured":"Klarquist, J. et al. Clonal expansion of vaccine-elicited T cells is independent of aerobic glycolysis. Sci. Immunol. 3, eaas9822 (2018).","journal-title":"Sci. Immunol."},{"key":"2034_CR20","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.immuni.2007.04.013","volume":"26","author":"VP Badovinac","year":"2007","unstructured":"Badovinac, V. P., Haring, J. S. & Harty, J. T. Initial T cell receptor transgenic cell precursor frequency dictates critical aspects of the CD8+ T cell response to infection. Immunity 26, 827\u2013841 (2007).","journal-title":"Immunity"},{"key":"2034_CR21","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/ni1227","volume":"6","author":"AL Marzo","year":"2005","unstructured":"Marzo, A. L. et al. Initial T cell frequency dictates memory CD8+ T cell lineage commitment. Nat. Immunol. 6, 793\u2013799 (2005).","journal-title":"Nat. Immunol."},{"key":"2034_CR22","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nmeth.4401","volume":"14","author":"AN Schep","year":"2017","unstructured":"Schep, A. N., Wu, B., Buenrostro, J. D. & Greenleaf, W. J. chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data. Nat. Methods 14, 975\u2013978 (2017).","journal-title":"Nat. Methods"},{"key":"2034_CR23","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.immuni.2016.10.028","volume":"45","author":"JP Scott-Browne","year":"2016","unstructured":"Scott-Browne, J. P. et al. Dynamic changes in chromatin accessibility occur in CD8+ T cells responding to viral infection. Immunity 45, 1327\u20131340 (2016).","journal-title":"Immunity"},{"key":"2034_CR24","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","volume":"27","author":"EJ Wherry","year":"2007","unstructured":"Wherry, E. J. et al. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity 27, 670\u2013684 (2007).","journal-title":"Immunity"},{"key":"2034_CR25","doi-asserted-by":"crossref","first-page":"3304","DOI":"10.1073\/pnas.0511137103","volume":"103","author":"CJ Luckey","year":"2006","unstructured":"Luckey, C. J. et al. Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells. Proc. Natl Acad. Sci. USA 103, 3304\u20133309 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2034_CR26","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545\u201315550 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2034_CR27","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.immuni.2022.02.004","volume":"55","author":"JR Giles","year":"2022","unstructured":"Giles, J. R. et al. Human epigenetic and transcriptional T cell differentiation atlas for identifying functional T cell-specific enhancers. Immunity 55, 557\u2013574 (2022).","journal-title":"Immunity"},{"key":"2034_CR28","doi-asserted-by":"crossref","unstructured":"Zhang, X. et al. Depletion of BATF in CAR-T cells enhances antitumor activity by inducing resistance against exhaustion and formation of central memory cells. Cancer Cell 40, 1407\u20131422.e7 (2022).","DOI":"10.1016\/j.ccell.2022.09.013"},{"key":"2034_CR29","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/s41590-021-00964-8","volume":"22","author":"H Seo","year":"2021","unstructured":"Seo, H. et al. BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells. Nat. Immunol. 22, 983\u2013995 (2021).","journal-title":"Nat. Immunol."},{"key":"2034_CR30","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41586-019-1805-z","volume":"576","author":"RC Lynn","year":"2019","unstructured":"Lynn, R. C. et al. c-Jun overexpression in CAR T cells induces exhaustion resistance. Nature 576, 293\u2013300 (2019).","journal-title":"Nature"},{"key":"2034_CR31","doi-asserted-by":"crossref","first-page":"eabo4997","DOI":"10.1126\/scitranslmed.abo4997","volume":"14","author":"V van der Heide","year":"2022","unstructured":"van der Heide, V., Humblin, E., Vaidya, A. & Kamphorst, A. O. Advancing beyond the twists and turns of T cell exhaustion in cancer. Sci. Transl. Med. 14, eabo4997 (2022).","journal-title":"Sci. Transl. Med."},{"key":"2034_CR32","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/s41586-019-0985-x","volume":"567","author":"J Chen","year":"2019","unstructured":"Chen, J. et al. NR4A transcription factors limit CAR T cell function in solid tumours. Nature 567, 530\u2013534 (2019).","journal-title":"Nature"},{"key":"2034_CR33","volume":"14","author":"IY Jung","year":"2022","unstructured":"Jung, I. Y. et al. BLIMP1 and NR4A3 transcription factors reciprocally regulate antitumor CAR T cell stemness and exhaustion. Sci. Transl. Med. 14, eabn7336 (2022).","journal-title":"Sci. Transl. Med."},{"key":"2034_CR34","volume":"8","author":"Z Bai","year":"2022","unstructured":"Bai, Z. et al. Single-cell antigen-specific landscape of CAR T infusion product identifies determinants of CD19-positive relapse in patients with ALL. Sci. Adv. 8, eabj2820 (2022).","journal-title":"Sci. Adv."},{"key":"2034_CR35","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1158\/2159-8290.CD-20-1677","volume":"11","author":"GM Chen","year":"2021","unstructured":"Chen, G. M. et al. Integrative bulk and single-cell profiling of premanufacture T-cell populations reveals factors mediating long-term persistence of CAR T-cell therapy. Cancer Discov. 11, 2186\u20132199 (2021).","journal-title":"Cancer Discov."},{"key":"2034_CR36","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1038\/s41591-020-1061-7","volume":"26","author":"Q Deng","year":"2020","unstructured":"Deng, Q. et al. Characteristics of anti-CD19 CAR T cell infusion products associated with efficacy and toxicity in patients with large B cell lymphomas. Nat. Med. 26, 1878\u20131887 (2020).","journal-title":"Nat. Med."},{"key":"2034_CR37","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1038\/s41587-023-01687-x","volume":"41","author":"DC Kirouac","year":"2023","unstructured":"Kirouac, D. C. et al. Deconvolution of clinical variance in CAR-T cell pharmacology and response. Nat. Biotechnol. 41, 1606\u20131617 (2023).","journal-title":"Nat. Biotechnol."},{"key":"2034_CR38","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-13880-1","volume":"11","author":"A Sheih","year":"2020","unstructured":"Sheih, A. et al. Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy. Nat. Commun. 11, 219 (2020).","journal-title":"Nat. Commun."},{"key":"2034_CR39","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41586-024-07242-1","volume":"629","author":"JD Chan","year":"2024","unstructured":"Chan, J. D. et al. FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy. Nature 629, 201\u2013210 (2024).","journal-title":"Nature"},{"key":"2034_CR40","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41586-024-07300-8","volume":"629","author":"AE Doan","year":"2024","unstructured":"Doan, A. E. et al. FOXO1 is a master regulator of memory programming in CAR T cells. Nature 629, 211\u2013218 (2024).","journal-title":"Nature"},{"key":"2034_CR41","doi-asserted-by":"crossref","first-page":"16472","DOI":"10.1073\/pnas.1407393111","volume":"111","author":"ND Pennock","year":"2014","unstructured":"Pennock, N. D., Gapin, L. & Kedl, R. M. IL-27 is required for shaping the magnitude, affinity distribution, and memory of T cells responding to subunit immunization. Proc. Natl Acad. Sci. USA 111, 16472\u201316477 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2034_CR42","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.4049\/jimmunol.178.3.1564","volume":"178","author":"PJ Sanchez","year":"2007","unstructured":"Sanchez, P. J., McWilliams, J. A., Haluszczak, C., Yagita, H. & Kedl, R. M. Combined TLR\/CD40 stimulation mediates potent cellular immunity by regulating dendritic cell expression of CD70 in vivo. J. Immunol. 178, 1564\u20131572 (2007).","journal-title":"J. Immunol."},{"key":"2034_CR43","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1016\/j.vaccine.2011.12.017","volume":"30","author":"PJ Sanchez","year":"2012","unstructured":"Sanchez, P. J. & Kedl, R. M. An alternative signal 3: CD8+ T cell memory independent of IL-12 and type I IFN is dependent on CD27\/OX40 signaling. Vaccine 30, 1154\u20131161 (2012).","journal-title":"Vaccine"},{"key":"2034_CR44","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1084\/jem.20031591","volume":"199","author":"CL Ahonen","year":"2004","unstructured":"Ahonen, C. L. et al. Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN. J. Exp. Med. 199, 775\u2013784 (2004).","journal-title":"J. Exp. Med."},{"key":"2034_CR45","doi-asserted-by":"crossref","first-page":"200814","DOI":"10.1016\/j.omton.2024.200814","volume":"32","author":"DH Quach","year":"2024","unstructured":"Quach, D. H. et al. Rejection resistant CD30.CAR-modified Epstein\u2013Barr virus-specific T cells as an off-the-shelf platform for CD30+ lymphoma. Mol. Ther. Oncol. 32, 200814 (2024).","journal-title":"Mol. Ther. Oncol."},{"key":"2034_CR46","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1182\/blood-2006-11-059139","volume":"110","author":"B Savoldo","year":"2007","unstructured":"Savoldo, B. et al. Epstein Barr virus specific cytotoxic T lymphocytes expressing the anti-CD30\u03b6 artificial chimeric T-cell receptor for immunotherapy of Hodgkin disease. Blood 110, 2620\u20132630 (2007).","journal-title":"Blood"},{"key":"2034_CR47","doi-asserted-by":"crossref","first-page":"6050","DOI":"10.1182\/blood-2011-05-354449","volume":"118","author":"CU Louis","year":"2011","unstructured":"Louis, C. U. et al. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood 118, 6050\u20136056 (2011).","journal-title":"Blood"},{"key":"2034_CR48","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1182\/blood-2011-07-366419","volume":"119","author":"S Terakura","year":"2012","unstructured":"Terakura, S. et al. Generation of CD19-chimeric antigen receptor modified CD8+ T cells derived from virus-specific central memory T cells. Blood 119, 72\u201382 (2012).","journal-title":"Blood"},{"key":"2034_CR49","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1182\/blood.V120.21.353.353","volume":"120","author":"KJ Curran","year":"2012","unstructured":"Curran, K. J. et al. CD19 targeted allogeneic EBV-specific T cells for the treatment of relapsed ALL in pediatric patients post HSCT. Blood 120, 353 (2012).","journal-title":"Blood"},{"key":"2034_CR50","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.adg1094","volume":"9","author":"SA Minnie","year":"2024","unstructured":"Minnie, S. A. et al. TIM-3+ CD8 T cells with a terminally exhausted phenotype retain functional capacity in hematological malignancies. Sci. Immunol. 9, eadg1094 (2024).","journal-title":"Sci. Immunol."},{"key":"2034_CR51","doi-asserted-by":"crossref","DOI":"10.1186\/1476-4598-11-27","volume":"11","author":"M Tandon","year":"2012","unstructured":"Tandon, M. et al. RUNX2 mediates epigenetic silencing of the bone morphogenetic protein-3B (BMP-3B\/GDF10) in lung cancer cells. Mol. Cancer 11, 27 (2012).","journal-title":"Mol. Cancer"},{"key":"2034_CR52","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.111315","volume":"40","author":"H Hojo","year":"2022","unstructured":"Hojo, H. et al. RUNX2 regulates chromatin accessibility to direct the osteoblast program at neonatal stages. Cell Rep. 40, 111315 (2022).","journal-title":"Cell Rep."},{"key":"2034_CR53","volume":"13","author":"L Wang","year":"2022","unstructured":"Wang, L. et al. TET enzymes regulate skeletal development through increasing chromatin accessibility of RUNX2 target genes. Nat. Commun. 13, 4709 (2022).","journal-title":"Nat. Commun."},{"key":"2034_CR54","doi-asserted-by":"crossref","first-page":"701924","DOI":"10.3389\/fimmu.2021.701924","volume":"12","author":"S Korinfskaya","year":"2021","unstructured":"Korinfskaya, S., Parameswaran, S., Weirauch, M. T. & Barski, A. RUNX transcription factors in T cells\u2014what is beyond thymic development? Front. Immunol. 12, 701924 (2021).","journal-title":"Front. Immunol."},{"key":"2034_CR55","doi-asserted-by":"crossref","first-page":"e2104758118","DOI":"10.1073\/pnas.2104758118","volume":"118","author":"DG Gennert","year":"2021","unstructured":"Gennert, D. G. et al. Dynamic chromatin regulatory landscape of human CAR T cell exhaustion. Proc. Natl Acad. Sci. USA 118, e2104758118 (2021).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2034_CR56","doi-asserted-by":"crossref","first-page":"3875","DOI":"10.1182\/blood-2010-01-265041","volume":"116","author":"JN Kochenderfer","year":"2010","unstructured":"Kochenderfer, J. N., Yu, Z., Frasheri, D., Restifo, N. P. & Rosenberg, S. A. Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. Blood 116, 3875\u20133886 (2010).","journal-title":"Blood"},{"key":"2034_CR57","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1097\/CJI.0b013e3181ac6138","volume":"32","author":"JN Kochenderfer","year":"2009","unstructured":"Kochenderfer, J. N. et al. Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor. J. Immunother. 32, 689\u2013702 (2009).","journal-title":"J. Immunother."},{"key":"2034_CR58","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nmeth.3047","volume":"11","author":"NE Sanjana","year":"2014","unstructured":"Sanjana, N. E., Shalem, O. & Zhang, F. Improved vectors and genome-wide libraries for CRISPR screening. Nat. Methods 11, 783\u2013784 (2014).","journal-title":"Nat. Methods"},{"key":"2034_CR59","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/nmeth.4396","volume":"14","author":"MR Corces","year":"2017","unstructured":"Corces, M. R. et al. An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat. Methods 14, 959\u2013962 (2017).","journal-title":"Nat. Methods"},{"key":"2034_CR60","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nature14590","volume":"523","author":"JD Buenrostro","year":"2015","unstructured":"Buenrostro, J. D. et al. Single-cell chromatin accessibility reveals principles of regulatory variation. Nature 523, 486\u2013490 (2015).","journal-title":"Nature"},{"key":"2034_CR61","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.12688\/f1000research.15931.1","volume":"7","author":"SW Wingett","year":"2018","unstructured":"Wingett, S. W. & Andrews, S. FastQ Screen: a tool for multi-genome mapping and quality control. F1000Res. 7, 1338 (2018).","journal-title":"F1000Res."},{"key":"2034_CR62","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","volume":"32","author":"P Ewels","year":"2016","unstructured":"Ewels, P., Magnusson, M., Lundin, S. & K\u00e4ller, M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics 32, 3047\u20133048 (2016).","journal-title":"Bioinformatics"},{"key":"2034_CR63","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15\u201321 (2013).","journal-title":"Bioinformatics"},{"key":"2034_CR64","volume":"15","author":"MI Love","year":"2014","unstructured":"Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).","journal-title":"Genome Biol."},{"key":"2034_CR65","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1093\/nar\/gkz622","volume":"47","author":"A Zhu","year":"2019","unstructured":"Zhu, A., Srivastava, A., Ibrahim, J. G., Patro, R. & Love, M. I. Nonparametric expression analysis using inferential replicate counts. Nucleic Acids Res. 47, e105 (2019).","journal-title":"Nucleic Acids Res."},{"key":"2034_CR66","volume":"10","author":"Y Zhou","year":"2019","unstructured":"Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).","journal-title":"Nat. Commun."},{"key":"2034_CR67","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","volume":"30","author":"A Kr\u00e4mer","year":"2014","unstructured":"Kr\u00e4mer, A., Green, J., Pollard, J.Jr & Tugendreich, S. Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics 30, 523\u2013530 (2014).","journal-title":"Bioinformatics"},{"key":"2034_CR68","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng1180","volume":"34","author":"VK Mootha","year":"2003","unstructured":"Mootha, V. K. et al. PGC-1\u03b1-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267\u2013273 (2003).","journal-title":"Nat. Genet."},{"key":"2034_CR69","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","volume":"26","author":"AR Quinlan","year":"2010","unstructured":"Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841\u2013842 (2010).","journal-title":"Bioinformatics"},{"key":"2034_CR70","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).","journal-title":"Nucleic Acids Res."},{"key":"2034_CR71","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","volume":"38","author":"S Heinz","year":"2010","unstructured":"Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576\u2013589 (2010).","journal-title":"Mol. Cell"},{"key":"2034_CR72","doi-asserted-by":"crossref","first-page":"W187","DOI":"10.1093\/nar\/gku365","volume":"42","author":"F Ram\u00edrez","year":"2014","unstructured":"Ram\u00edrez, F., D\u00fcndar, F., Diehl, S., Gr\u00fcning, B. A. & Manke, T. deepTools: a flexible platform for exploring deep-sequencing data. Nucleic Acids Res. 42, W187\u2013W191 (2014).","journal-title":"Nucleic Acids Res."}],"container-title":["Nature Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41590-024-02034-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-024-02034-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-024-02034-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T21:15:39Z","timestamp":1735852539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41590-024-02034-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":72,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["2034"],"URL":"https:\/\/doi.org\/10.1038\/s41590-024-02034-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3712137\/v1","asserted-by":"object"}]},"ISSN":["1529-2908","1529-2916"],"issn-type":[{"value":"1529-2908","type":"print"},{"value":"1529-2916","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"5 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The University of Colorado Anschutz Medical Campus has filed a patent application, PCT\/US2024\/054159, regarding compositions and methods of enhancing immune cell therapies by RUNX2 modulation, with K.R.D., J.P.S.-B. and T.J.F. listed as inventors. The other authors have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}