{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:57:18Z","timestamp":1790863038787,"version":"4.1.0"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Immunol"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1038\/s41590-026-02419-4","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:03:24Z","timestamp":1770717804000},"page":"530-542","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Flt3L-mediated tumor cDC1 expansion enhances immunotherapy by priming stem-like CD8+ T\u2009cells in lymph nodes"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5884-2786","authenticated-orcid":false,"given":"Junyun","family":"Lai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheok Weng","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse D.","family":"Armitage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine M.","family":"Audsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Kuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7191-3948","authenticated-orcid":false,"given":"Emily B.","family":"Derrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3410-281X","authenticated-orcid":false,"given":"Laura S.","family":"Carstensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3731-6204","authenticated-orcid":false,"given":"Christina M.","family":"Scheffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt E.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4634-7600","authenticated-orcid":false,"given":"Kevin","family":"Sek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Principe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9213-6180","authenticated-orcid":false,"given":"Joelle S.","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran G.","family":"House","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1388-9510","authenticated-orcid":false,"given":"Amanda X. Y.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5009-9895","authenticated-orcid":false,"given":"Kah Min","family":"Yap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Middelburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-5696","authenticated-orcid":false,"given":"Isabelle","family":"Munoz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0702-0446","authenticated-orcid":false,"given":"Dat","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junming","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thang X.","family":"Hoang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3903-166X","authenticated-orcid":false,"given":"Kirsten L.","family":"Todd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2105-1160","authenticated-orcid":false,"given":"Maximilien","family":"Evrard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-2708","authenticated-orcid":false,"given":"Jonathan","family":"Chee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8496-6632","authenticated-orcid":false,"given":"Laura K.","family":"Mackay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair R. R.","family":"Forrest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3528-478X","authenticated-orcid":false,"given":"Ian A.","family":"Parish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4335-615X","authenticated-orcid":false,"given":"Anthony","family":"Bosco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4940-0155","authenticated-orcid":false,"given":"Jason","family":"Waithman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2116-013X","authenticated-orcid":false,"given":"Paul A.","family":"Beavis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5303-9561","authenticated-orcid":false,"given":"Phillip K.","family":"Darcy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"2419_CR1","doi-asserted-by":"publisher","first-page":"2174","DOI":"10.1093\/annonc\/mdt161","volume":"24","author":"JD Wolchok","year":"2013","unstructured":"Wolchok, J. D. et al. Four-year survival rates for patients with metastatic melanoma who received ipilimumab in phase\u2009II clinical trials. Ann. Oncol. 24, 2174\u20132180 (2013).","journal-title":"Ann. Oncol."},{"key":"2419_CR2","doi-asserted-by":"publisher","first-page":"1960","DOI":"10.1126\/science.1129139","volume":"313","author":"J Galon","year":"2006","unstructured":"Galon, J. et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313, 1960\u20131964 (2006).","journal-title":"Science"},{"key":"2419_CR3","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.immuni.2018.12.021","volume":"50","author":"I Siddiqui","year":"2019","unstructured":"Siddiqui, I. et al. Intratumoral Tcf1+ PD-1+ CD8+ T\u2009cells with stem-like properties promote tumor control in response to vaccination and checkpoint blockade immunotherapy. Immunity 50, 195\u2013211 (2019).","journal-title":"Immunity"},{"key":"2419_CR4","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.cell.2018.10.038","volume":"175","author":"M Sade-Feldman","year":"2018","unstructured":"Sade-Feldman, M. et al. Defining T cell states associated with response to checkpoint immunotherapy in melanoma. Cell 175, 998\u20131013 (2018).","journal-title":"Cell"},{"key":"2419_CR5","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/s41568-023-00615-0","volume":"23","author":"T Gebhardt","year":"2023","unstructured":"Gebhardt, T., Park, S. L. & Parish, I. A. Stem-like exhausted and memory CD8+ T\u2009cells in cancer. Nat. Rev. Cancer 23, 780\u2013798 (2023).","journal-title":"Nat. Rev. Cancer"},{"key":"2419_CR6","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/nature22079","volume":"545","author":"AC Huang","year":"2017","unstructured":"Huang, A. C. et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature 545, 60\u201365 (2017).","journal-title":"Nature"},{"key":"2419_CR7","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nature19330","volume":"537","author":"SJ Im","year":"2016","unstructured":"Im, S. J. et al. Defining CD8+ T\u2009cells that provide the proliferative burst after PD-1 therapy. Nature 537, 417\u2013421 (2016).","journal-title":"Nature"},{"key":"2419_CR8","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.immuni.2018.11.014","volume":"50","author":"S Kurtulus","year":"2019","unstructured":"Kurtulus, S. et al. Checkpoint blockade immunotherapy induces dynamic changes in PD-1\u2212CD8+ tumor-infiltrating T\u2009cells. Immunity 50, 181\u2013194 (2019).","journal-title":"Immunity"},{"key":"2419_CR9","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41586-019-1836-5","volume":"576","author":"CS Jansen","year":"2019","unstructured":"Jansen, C. S. et al. An intra-tumoral niche maintains and differentiates stem-like CD8 T\u2009cells. Nature 576, 465\u2013470 (2019).","journal-title":"Nature"},{"key":"2419_CR10","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41590-019-0312-6","volume":"20","author":"BC Miller","year":"2019","unstructured":"Miller, B. C. et al. Subsets of exhausted CD8+ T\u2009cells differentially mediate tumor control and respond to checkpoint blockade. Nat. Immunol. 20, 326\u2013336 (2019).","journal-title":"Nat. Immunol."},{"key":"2419_CR11","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.immuni.2020.04.014","volume":"52","author":"JC Beltra","year":"2020","unstructured":"Beltra, J. C. et al. Developmental relationships of four exhausted CD8+ T\u2009cell subsets reveals underlying transcriptional and epigenetic landscape control mechanisms. Immunity 52, 825\u2013841 (2020).","journal-title":"Immunity"},{"key":"2419_CR12","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1126\/science.aaf2807","volume":"354","author":"KE Pauken","year":"2016","unstructured":"Pauken, K. E. et al. Epigenetic stability of exhausted T\u2009cells limits durability of reinvigoration by PD-1 blockade. Science 354, 1160\u20131165 (2016).","journal-title":"Science"},{"key":"2419_CR13","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/nature22367","volume":"545","author":"M Philip","year":"2017","unstructured":"Philip, M. et al. Chromatin states define tumour-specific T\u2009cell dysfunction and reprogramming. Nature 545, 452\u2013456 (2017).","journal-title":"Nature"},{"key":"2419_CR14","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/s41586-021-03862-z","volume":"597","author":"CS Eberhardt","year":"2021","unstructured":"Eberhardt, C. S. et al. Functional HPV-specific PD-1+ stem-like CD8 T cells in head and neck cancer. Nature 597, 279\u2013284 (2021).","journal-title":"Nature"},{"key":"2419_CR15","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.ccell.2014.09.007","volume":"26","author":"ML Broz","year":"2014","unstructured":"Broz, M. L. et al. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T\u2009cell immunity. Cancer Cell 26, 638\u2013652 (2014).","journal-title":"Cancer Cell"},{"key":"2419_CR16","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/j.immuni.2016.03.012","volume":"44","author":"H Salmon","year":"2016","unstructured":"Salmon, H. et al. Expansion and activation of CD103+ dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition. Immunity 44, 924\u2013938 (2016).","journal-title":"Immunity"},{"key":"2419_CR17","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1016\/j.cell.2018.01.004","volume":"172","author":"JP Bottcher","year":"2018","unstructured":"Bottcher, J. P. et al. NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell 172, 1022\u20131037 (2018).","journal-title":"Cell"},{"key":"2419_CR18","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.1016\/j.ccell.2023.06.008","volume":"41","author":"P Meiser","year":"2023","unstructured":"Meiser, P. et al. A distinct stimulatory cDC1 subpopulation amplifies CD8+ T\u2009cell responses in tumors for protective anti-cancer immunity. Cancer Cell 41, 1498\u20131515 (2023).","journal-title":"Cancer Cell"},{"key":"2419_CR19","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.ccell.2017.04.003","volume":"31","author":"S Spranger","year":"2017","unstructured":"Spranger, S., Dai, D., Horton, B. & Gajewski, T. F. Tumor-residing Batf3 dendritic cells are required for effector t cell trafficking and adoptive T\u2009cell therapy. Cancer Cell 31, 711\u2013723 (2017).","journal-title":"Cancer Cell"},{"key":"2419_CR20","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.immuni.2022.03.006","volume":"55","author":"S D\u00e4hling","year":"2022","unstructured":"D\u00e4hling, S. et al. Type 1 conventional dendritic cells maintain and guide the differentiation of precursors of exhausted T\u2009cells in distinct cellular niches. Immunity 55, 656\u2013670 (2022).","journal-title":"Immunity"},{"key":"2419_CR21","doi-asserted-by":"publisher","first-page":"2338","DOI":"10.1016\/j.immuni.2021.08.026","volume":"54","author":"JM Schenkel","year":"2021","unstructured":"Schenkel, J. M. et al. Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T\u2009cells in tumor-draining lymph nodes. Immunity 54, 2338\u20132353 (2021).","journal-title":"Immunity"},{"key":"2419_CR22","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1038\/s41590-020-0676-7","volume":"21","author":"J Lai","year":"2020","unstructured":"Lai, J. et al. Adoptive cellular therapy with T\u2009cells expressing the dendritic cell growth factor Flt3L drives epitope spreading and antitumor immunity. Nat. Immunol. 21, 914\u2013926 (2020).","journal-title":"Nat. Immunol."},{"key":"2419_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101256","volume":"4","author":"P Regnier","year":"2023","unstructured":"Regnier, P. et al. FLT3L-dependent dendritic cells control tumor immunity by modulating Treg and NK cell homeostasis. Cell Rep. Med. 4, 101256 (2023).","journal-title":"Cell Rep. Med."},{"key":"2419_CR24","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41586-020-2134-y","volume":"580","author":"B Maier","year":"2020","unstructured":"Maier, B. et al. A conserved dendritic-cell regulatory program limits antitumour immunity. Nature 580, 257\u2013262 (2020).","journal-title":"Nature"},{"key":"2419_CR25","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/j.immuni.2019.11.002","volume":"51","author":"WH Hudson","year":"2019","unstructured":"Hudson, W. H. et al. Proliferating transitory T\u2009cells with an effector-like transcriptional signature emerge from PD-1+ stem-like CD8+ T\u2009cells during chronic infection. Immunity 51, 1043\u20131058 (2019).","journal-title":"Immunity"},{"key":"2419_CR26","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1038\/s41586-022-05105-1","volume":"609","author":"C Tsui","year":"2022","unstructured":"Tsui, C. et al. MYB orchestrates T\u2009cell exhaustion and response to checkpoint inhibition. Nature 609, 354\u2013360 (2022).","journal-title":"Nature"},{"key":"2419_CR27","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1038\/s43018-020-00143-y","volume":"1","author":"N Bhardwaj","year":"2020","unstructured":"Bhardwaj, N. et al. Flt3 ligand augments immune responses to anti-DEC-205-NY-ESO-1 vaccine through expansion of dendritic cell subsets. Nat. Cancer 1, 1204\u20131217 (2020).","journal-title":"Nat. Cancer"},{"key":"2419_CR28","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nature07657","volume":"458","author":"D Zehn","year":"2009","unstructured":"Zehn, D., Lee, S. Y. & Bevan, M. J. Complete but curtailed T-cell response to very low-affinity antigen. Nature 458, 211\u2013214 (2009).","journal-title":"Nature"},{"key":"2419_CR29","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1038\/s41590-022-01337-5","volume":"23","author":"B Daniel","year":"2022","unstructured":"Daniel, B. et al. Divergent clonal differentiation trajectories of T\u2009cell exhaustion. Nat. Immunol. 23, 1614\u20131627 (2022).","journal-title":"Nat. Immunol."},{"key":"2419_CR30","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.immuni.2022.12.002","volume":"56","author":"N Prokhnevska","year":"2023","unstructured":"Prokhnevska, N. et al. CD8+ T\u2009cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor. Immunity 56, 107\u2013124 (2023).","journal-title":"Immunity"},{"key":"2419_CR31","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abg7836","volume":"6","author":"KA Connolly","year":"2021","unstructured":"Connolly, K. A. et al. A reservoir of stem-like CD8+ T\u2009cells in the tumor-draining lymph node preserves the ongoing antitumor immune response. Sci Immunol. 6, eabg7836 (2021).","journal-title":"Sci Immunol."},{"key":"2419_CR32","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/s41586-025-09212-7","volume":"644","author":"AXY Chen","year":"2025","unstructured":"Chen, A. X. Y. et al. Rewiring endogenous genes in CAR T\u2009cells for tumour-restricted payload delivery. Nature 644, 241\u2013251 (2025).","journal-title":"Nature"},{"key":"2419_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-59021-9","volume":"16","author":"K Sek","year":"2025","unstructured":"Sek, K. et al. Tumor site-directed A1R expression enhances CAR T\u2009cell function and improves efficacy against solid tumors. Nat. Commun. 16, 6123 (2025).","journal-title":"Nat. Commun."},{"key":"2419_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.113793","volume":"43","author":"IG House","year":"2024","unstructured":"House, I. G. et al. CRISPR\u2013Cas9 screening identifies an IRF1-SOCS1-mediated negative feedback loop that limits CXCL9 expression and antitumor immunity. Cell Rep. 43, 113793 (2024).","journal-title":"Cell Rep."},{"key":"2419_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32567-8","volume":"13","author":"RM Zemek","year":"2022","unstructured":"Zemek, R. M. et al. Temporally restricted activation of IFNbeta signaling underlies response to immune checkpoint therapy in mice. Nat. Commun. 13, 4895 (2022).","journal-title":"Nat. Commun."},{"key":"2419_CR36","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/s41590-024-02044-z","volume":"26","author":"S Singhaviranon","year":"2025","unstructured":"Singhaviranon, S., Dempsey, J. P., Hagymasi, A. T., Mandoiu, I. I. & Srivastava, P. K. Low-avidity T\u2009cells drive endogenous tumor immunity in mice and humans. Nat. Immunol. 26, 240\u2013251 (2025).","journal-title":"Nat. Immunol."},{"key":"2419_CR37","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1038\/s41590-024-02027-0","volume":"26","author":"Z Zhang","year":"2025","unstructured":"Zhang, Z. et al. Efficacy of CTLA-4 checkpoint therapy is dependent on IL-21 signaling to mediate cytotoxic reprogramming of PD-1+CD8+ T\u2009cells. Nat. Immunol. 26, 92\u2013104 (2025).","journal-title":"Nat. Immunol."},{"key":"2419_CR38","doi-asserted-by":"publisher","first-page":"6101","DOI":"10.1016\/j.cell.2021.11.007","volume":"184","author":"C Cui","year":"2021","unstructured":"Cui, C. et al. Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T\u2009cell responses. Cell 184, 6101\u20136118 (2021).","journal-title":"Cell"},{"key":"2419_CR39","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1038\/s41591-023-02345-0","volume":"29","author":"A Magen","year":"2023","unstructured":"Magen, A. et al. Intratumoral dendritic cell-CD4+ T helper cell niches enable CD8+ T cell differentiation following PD-1 blockade in hepatocellular carcinoma. Nat. Med. 29, 1389\u20131399 (2023).","journal-title":"Nat. Med."},{"key":"2419_CR40","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1038\/s41590-024-01792-2","volume":"25","author":"JH Chen","year":"2024","unstructured":"Chen, J. H. et al. Human lung cancer harbors spatially organized stem-immunity hubs associated with response to immunotherapy. Nat. Immunol. 25, 644\u2013658 (2024).","journal-title":"Nat. Immunol."},{"key":"2419_CR41","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.cell.2023.02.021","volume":"186","author":"MK Rahim","year":"2023","unstructured":"Rahim, M. K. et al. Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes. Cell 186, 1127\u20131143 (2023).","journal-title":"Cell"},{"key":"2419_CR42","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.immuni.2022.12.002","volume":"56","author":"N Prokhnevska","year":"2023","unstructured":"Prokhnevska, N. et al. CD8+ T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor. Immunity 56, 107\u2013124 (2023).","journal-title":"Immunity"},{"key":"2419_CR43","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abg7836","volume":"6","author":"KA Connolly","year":"2021","unstructured":"Connolly, K. A. et al. A reservoir of stem-like CD8+ T\u2009cells in the tumor-draining lymph node preserves the ongoing antitumor immune response. Sci. Immunol. 6, eabg7836 (2021).","journal-title":"Sci. Immunol."},{"key":"2419_CR44","doi-asserted-by":"publisher","first-page":"4049","DOI":"10.1016\/j.cell.2022.09.020","volume":"185","author":"Q Huang","year":"2022","unstructured":"Huang, Q. et al. The primordial differentiation of tumor-specific memory CD8+ T\u2009cells as bona fide responders to PD-1\/PD-L1 blockade in draining lymph nodes. Cell 185, 4049\u20134066 (2022).","journal-title":"Cell"},{"key":"2419_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46685-y","volume":"15","author":"L Lopez","year":"2024","unstructured":"Lopez, L. et al. Dendritic cell-targeted therapy expands CD8 T\u2009cell responses to bona-fide neoantigens in lung tumors. Nat. Commun. 15, 2280 (2024).","journal-title":"Nat. Commun."},{"key":"2419_CR46","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1158\/2159-8290.CD-16-0828","volume":"7","author":"V Anagnostou","year":"2017","unstructured":"Anagnostou, V. et al. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov. 7, 264\u2013276 (2017).","journal-title":"Cancer Discov."},{"key":"2419_CR47","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nature18945","volume":"536","author":"EM Verdegaal","year":"2016","unstructured":"Verdegaal, E. M. et al. Neoantigen landscape dynamics during human melanoma\u2013T\u2009cell interactions. Nature 536, 91\u201395 (2016).","journal-title":"Nature"},{"key":"2419_CR48","doi-asserted-by":"publisher","first-page":"4996","DOI":"10.1016\/j.cell.2021.08.020","volume":"184","author":"ML Burger","year":"2021","unstructured":"Burger, M. L. et al. Antigen dominance hierarchies shape TCF1+ progenitor CD8 T\u2009cell phenotypes in tumors. Cell 184, 4996\u20135014 (2021).","journal-title":"Cell"},{"key":"2419_CR49","doi-asserted-by":"publisher","first-page":"e007114","DOI":"10.1136\/jitc-2023-007114","volume":"11","author":"G Sugiyarto","year":"2023","unstructured":"Sugiyarto, G. et al. Reactivation of low avidity tumor-specific CD8+ T cells associates with immunotherapeutic efficacy of anti-PD-1. J. Immunother. Cancer 11, e007114 (2023).","journal-title":"J. Immunother. Cancer"},{"key":"2419_CR50","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1038\/s41586-024-07962-4","volume":"634","author":"B Feng","year":"2024","unstructured":"Feng, B. et al. The type 2 cytokine Fc-IL-4 revitalizes exhausted CD8+ T\u2009cells against cancer. Nature 634, 712\u2013720 (2024).","journal-title":"Nature"},{"key":"2419_CR51","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1038\/s41586-024-07762-w","volume":"634","author":"Z Bai","year":"2024","unstructured":"Bai, Z. et al. Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission. Nature 634, 702\u2013711 (2024).","journal-title":"Nature"},{"key":"2419_CR52","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111647","volume":"41","author":"W Chen","year":"2022","unstructured":"Chen, W. et al. Chronic type\u2009I interferon signaling promotes lipid-peroxidation-driven terminal CD8+ T\u2009cell exhaustion and curtails anti-PD-1 efficacy. Cell Rep. 41, 111647 (2022).","journal-title":"Cell Rep."},{"key":"2419_CR53","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.ccell.2019.01.003","volume":"35","author":"TN Gide","year":"2019","unstructured":"Gide, T. N. et al. Distinct immune cell populations define response to anti-PD-1 monotherapy and anti-PD-1\/anti-CTLA-4 combined therapy. Cancer Cell 35, 238\u2013255 (2019).","journal-title":"Cancer Cell"},{"key":"2419_CR54","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1038\/s41401-023-01079-6","volume":"44","author":"SA Kovacs","year":"2023","unstructured":"Kovacs, S. A., Fekete, J. T. & Gyorffy, B. Predictive biomarkers of immunotherapy response with pharmacological applications in solid tumors. Acta Pharmacol. Sin. 44, 1879\u20131889 (2023).","journal-title":"Acta Pharmacol. Sin."},{"key":"2419_CR55","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","volume":"42","author":"Y Hao","year":"2024","unstructured":"Hao, Y. et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol. 42, 293\u2013304 (2024).","journal-title":"Nat. Biotechnol."},{"key":"2419_CR56","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1038\/s41592-019-0433-8","volume":"16","author":"CS McGinnis","year":"2019","unstructured":"McGinnis, C. S. et al. MULTI-seq: sample multiplexing for single-cell RNA sequencing using lipid-tagged indices. Nat. Methods 16, 619\u2013626 (2019).","journal-title":"Nat. Methods"},{"key":"2419_CR57","doi-asserted-by":"publisher","first-page":"47","DOI":"10.12688\/f1000research.22139.1","volume":"9","author":"N Borcherding","year":"2020","unstructured":"Borcherding, N., Bormann, N. L. & Kraus, G. scRepertoire: an R-based toolkit for single-cell immune receptor analysis. F1000Res 9, 47 (2020).","journal-title":"F1000Res"},{"key":"2419_CR58","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","volume":"20","author":"D Aran","year":"2019","unstructured":"Aran, D. et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat. Immunol. 20, 163\u2013172 (2019).","journal-title":"Nat. Immunol."},{"key":"2419_CR59","doi-asserted-by":"publisher","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":"2419_CR60","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nbt.2859","volume":"32","author":"C Trapnell","year":"2014","unstructured":"Trapnell, C. et al. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat. Biotechnol. 32, 381\u2013386 (2014).","journal-title":"Nat. Biotechnol."},{"key":"2419_CR61","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","volume":"566","author":"J Cao","year":"2019","unstructured":"Cao, J. et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature 566, 496\u2013502 (2019).","journal-title":"Nature"},{"key":"2419_CR62","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23324-4","volume":"12","author":"M Andreatta","year":"2021","unstructured":"Andreatta, M. et al. Interpretation of T\u2009cell states from single-cell transcriptomics data using reference atlases. Nat. Commun. 12, 2965 (2021).","journal-title":"Nat. Commun."},{"key":"2419_CR63","doi-asserted-by":"publisher","first-page":"2988","DOI":"10.1016\/j.cell.2021.04.038","volume":"184","author":"A Obradovic","year":"2021","unstructured":"Obradovic, A. et al. Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages. Cell 184, 2988\u20133005 (2021).","journal-title":"Cell"},{"key":"2419_CR64","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/nature25501","volume":"554","author":"S Mariathasan","year":"2018","unstructured":"Mariathasan, S. et al. TGF\u03b2 attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 554, 544\u2013548 (2018).","journal-title":"Nature"},{"key":"2419_CR65","first-page":"100625","volume":"5","author":"B Gy\u0151rffy","year":"2024","unstructured":"Gy\u0151rffy, B. Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors. Innovation (Camb.) 5, 100625 (2024).","journal-title":"Innovation (Camb.)"},{"key":"2419_CR66","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1111\/bph.16257","volume":"181","author":"B Gyorffy","year":"2024","unstructured":"Gyorffy, B. Transcriptome-level discovery of survival-associated biomarkers and therapy targets in non-small-cell lung cancer. Br. J. Pharmacol. 181, 362\u2013374 (2024).","journal-title":"Br. J. Pharmacol."}],"container-title":["Nature Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41590-026-02419-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-026-02419-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-026-02419-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T21:02:18Z","timestamp":1772571738000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41590-026-02419-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,10]]},"references-count":66,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["2419"],"URL":"https:\/\/doi.org\/10.1038\/s41590-026-02419-4","relation":{},"ISSN":["1529-2908","1529-2916"],"issn-type":[{"value":"1529-2908","type":"print"},{"value":"1529-2916","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,10]]},"assertion":[{"value":"16 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"P.A.B. declares research funding from Bristol-Myers-Squibb. P.K.D. declares research funding from CREATE Medicines, Prescient Therapeutics, Bristol-Myers-Squibb and INOVIQ. I.A.P. declares research funding from AstraZeneca, Bristol-Myers-Squibb and Roche Genentech. P.A.B. and P.K.D. declare the following patent related to this work. PCT\/AU2019\/050660 \u2018Modified T\u2009cells and uses thereof.\u2019 The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}