{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T18:27:26Z","timestamp":1786991246746,"version":"build-2736575974"},"posted":{"date-parts":[[2026,1,18]]},"group-title":"Oncology","reference-count":122,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"id":[{"id":"https:\/\/ror.org\/05sjnvv07","id-type":"ROR","asserted-by":"publisher"}]},{"award":["U2C-CA233238"],"award-info":[{"award-number":["U2C-CA233238"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000092","name":"United States National Library of Medicine","doi-asserted-by":"crossref","award":["R01LM013154"],"award-info":[{"award-number":["R01LM013154"]}],"id":[{"id":"10.13039\/100000092","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NCI Informatics Technology for Cancer Research","award":["U01CA220413"],"award-info":[{"award-number":["U01CA220413"]}]},{"DOI":"10.13039\/100014989","name":"Chan Zuckerberg Initiative","doi-asserted-by":"crossref","award":["2022-249297(5022)"],"award-info":[{"award-number":["2022-249297(5022)"]}],"id":[{"id":"10.13039\/100014989","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Regional lymph nodes (LNs) in the thoracic cavity are essential immunological hubs that coordinate humoral and cell-mediated immunity during non-small cell lung cancer (NSCLC) progression. To investigate immune dysregulation in non-metastatic regional LNs from patients with advanced-stage NSCLC, we performed multimodal profiling of 36 LNs from 11 patients undergoing curative-intent resection using CITE-seq, scRNA-seq, and Imaging Mass Cytometry (IMC). Regional N1 LNs from our advanced-stage patients (stage IB\u2013IIIA) displayed visceral pleural invasion (VPI) or lymphovascular invasion (LVI), and exhibited significant enrichment of dysfunctional CD8\u207a T cells and regulatory T cells compared with N2 LNs and stage IA LNs. These subsets spatially co-localized with mature regulatory dendritic cells (CD1c\u207a, TIM3\u207a, LAMP3\u207a), forming an immunosuppressive niche enriched in advance-stage N1 LNs. Concurrently, advanced-stage N1 LNs contained more \u201cdecorticated\u201d B-cell follicles characterized by decreased encapsulation of the mantle zone layer surrounding the germinal centers. Together, these findings reveal parallel disruption of humoral and cell-mediated immunity in regional LNs of advanced-stage NSCLC patients.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>This manuscript demonstrates that non-metastatic regional lymph nodes in advanced NSCLC are not immunologically normal but instead show coordinated remodeling of T cell immunity and B-cell follicular architecture. By integrating single-cell and spatial profiling, it identifies dysfunctional CD8 T cells, regulatory T cells, mregDC-associated suppressive niches, and disrupted follicular organization as features of early nodal immune dysregulation before overt metastasis. These findings support regional lymph nodes as clinically relevant immune sites that may improve risk stratification and guide future perioperative or adjuvant immunotherapy strategies in resected NSCLC.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.12.25343268","type":"posted-content","created":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T20:10:15Z","timestamp":1768767015000},"source":"Crossref","is-referenced-by-count":1,"title":["Multimodal single-cell spatial profiling reveals altered T cell immunity and B-cell follicular architecture in non-metastatic lymph nodes of advanced NSCLC patients"],"prefix":"10.64898","author":[{"given":"Zhan Hao","family":"Xi","sequence":"first","affiliation":[{"name":"Department of Medicine, Section of Computational Biomedicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Computational Biomedicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"McDermott","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Computational Biomedicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E.","family":"Kane","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Computational Biomedicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxanna","family":"Pfefferkorn","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Computational Biomedicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehab","family":"Billatos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Computational Biomedicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"},{"name":"Department of Medicine, Section of Pulmonary and Critical Care Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Hosking","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Beane","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Computational Biomedicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3122-2875","authenticated-orcid":false,"given":"Eric J.","family":"Burks","sequence":"additional","affiliation":[{"name":"Department of Pathology & Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston Medical Center, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"Mazzilli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Computational Biomedicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Suzuki","sequence":"additional","affiliation":[{"name":"INOVA, Department of Surgery, Division of Thoracic Surgery, Falls Church, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Campbell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Computational Biomedicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081710401257000_2026.01.12.25343268v2.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"2026081710401257000_2026.01.12.25343268v2.2","unstructured":"Cancer of the Lung and Bronchus - Cancer Stat Facts. SEER. Accessed February 9, 2023. https:\/\/seer.cancer.gov\/statfacts\/html\/lungb.html"},{"key":"2026081710401257000_2026.01.12.25343268v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2024.05.026"},{"key":"2026081710401257000_2026.01.12.25343268v2.4","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-40389-2"},{"key":"2026081710401257000_2026.01.12.25343268v2.5","unstructured":"Asamura H . Staging Manual in Thoracic Oncology 3rd Edition. Published online 2024."},{"key":"2026081710401257000_2026.01.12.25343268v2.6","doi-asserted-by":"publisher","DOI":"10.1097\/LBR.0000000000000545"},{"key":"2026081710401257000_2026.01.12.25343268v2.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00347-z"},{"key":"2026081710401257000_2026.01.12.25343268v2.8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1183286"},{"key":"2026081710401257000_2026.01.12.25343268v2.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2021.07.003"},{"key":"2026081710401257000_2026.01.12.25343268v2.10","doi-asserted-by":"publisher","DOI":"10.1038\/nri3818"},{"key":"2026081710401257000_2026.01.12.25343268v2.11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01643"},{"key":"2026081710401257000_2026.01.12.25343268v2.12","unstructured":"Bhandarkar V , Dinter T , Spranger S . Architects of immunity: How dendritic cells shape CD8+ T cell fate in cancer. Science Immunology. Published online 2025."},{"key":"2026081710401257000_2026.01.12.25343268v2.13","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-04807-0"},{"key":"2026081710401257000_2026.01.12.25343268v2.14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.666233"},{"key":"2026081710401257000_2026.01.12.25343268v2.15","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00301-w"},{"key":"2026081710401257000_2026.01.12.25343268v2.16","doi-asserted-by":"publisher","DOI":"10.1101\/2025.06.26.661765"},{"key":"2026081710401257000_2026.01.12.25343268v2.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.04.019"},{"key":"2026081710401257000_2026.01.12.25343268v2.18","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00017"},{"key":"2026081710401257000_2026.01.12.25343268v2.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.052"},{"key":"2026081710401257000_2026.01.12.25343268v2.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17046-2"},{"key":"2026081710401257000_2026.01.12.25343268v2.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.04.003"},{"key":"2026081710401257000_2026.01.12.25343268v2.22","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-022-00689-z"},{"key":"2026081710401257000_2026.01.12.25343268v2.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0221-9"},{"key":"2026081710401257000_2026.01.12.25343268v2.24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1507501"},{"key":"2026081710401257000_2026.01.12.25343268v2.25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1658848"},{"key":"2026081710401257000_2026.01.12.25343268v2.26","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14184374"},{"key":"2026081710401257000_2026.01.12.25343268v2.27","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15082250"},{"key":"2026081710401257000_2026.01.12.25343268v2.28","unstructured":"You S . Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity."},{"key":"2026081710401257000_2026.01.12.25343268v2.29","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-025-04180-3"},{"key":"2026081710401257000_2026.01.12.25343268v2.30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1422206"},{"key":"2026081710401257000_2026.01.12.25343268v2.31","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2024.2392898"},{"key":"2026081710401257000_2026.01.12.25343268v2.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101448"},{"key":"2026081710401257000_2026.01.12.25343268v2.33","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-024-12587-x"},{"key":"2026081710401257000_2026.01.12.25343268v2.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.101934"},{"key":"2026081710401257000_2026.01.12.25343268v2.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-64980-y"},{"key":"2026081710401257000_2026.01.12.25343268v2.36","doi-asserted-by":"publisher","DOI":"10.1101\/113068"},{"key":"2026081710401257000_2026.01.12.25343268v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2869"},{"key":"2026081710401257000_2026.01.12.25343268v2.38","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1032"},{"key":"2026081710401257000_2026.01.12.25343268v2.39","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2302983"},{"key":"2026081710401257000_2026.01.12.25343268v2.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01224-2"},{"key":"2026081710401257000_2026.01.12.25343268v2.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.08.2295"},{"key":"2026081710401257000_2026.01.12.25343268v2.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2021.09.005"},{"key":"2026081710401257000_2026.01.12.25343268v2.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01048-4"},{"key":"2026081710401257000_2026.01.12.25343268v2.44","doi-asserted-by":"publisher","DOI":"10.1038\/ni1582"},{"key":"2026081710401257000_2026.01.12.25343268v2.45","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11947-7"},{"key":"2026081710401257000_2026.01.12.25343268v2.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.04.014"},{"key":"2026081710401257000_2026.01.12.25343268v2.47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1568590"},{"key":"2026081710401257000_2026.01.12.25343268v2.48","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2008.15"},{"key":"2026081710401257000_2026.01.12.25343268v2.49","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-00990-6"},{"key":"2026081710401257000_2026.01.12.25343268v2.50","unstructured":"Human dendritic cells in cancer. SCIENCE IMMUNOLOGY. Published online 2022."},{"key":"2026081710401257000_2026.01.12.25343268v2.51","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-025-00831-x"},{"key":"2026081710401257000_2026.01.12.25343268v2.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.02.021"},{"key":"2026081710401257000_2026.01.12.25343268v2.53","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1199"},{"key":"2026081710401257000_2026.01.12.25343268v2.54","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16122211"},{"key":"2026081710401257000_2026.01.12.25343268v2.55","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58289-1"},{"key":"2026081710401257000_2026.01.12.25343268v2.56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01014"},{"key":"2026081710401257000_2026.01.12.25343268v2.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.06.010"},{"key":"2026081710401257000_2026.01.12.25343268v2.58","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.217"},{"key":"2026081710401257000_2026.01.12.25343268v2.59","doi-asserted-by":"publisher","DOI":"10.1038\/ni1332"},{"key":"2026081710401257000_2026.01.12.25343268v2.60","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01060-7"},{"key":"2026081710401257000_2026.01.12.25343268v2.61","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00493-5"},{"key":"2026081710401257000_2026.01.12.25343268v2.62","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05706-4"},{"key":"2026081710401257000_2026.01.12.25343268v2.63","doi-asserted-by":"publisher","DOI":"10.1038\/nature14664"},{"key":"2026081710401257000_2026.01.12.25343268v2.64","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01576-4"},{"key":"2026081710401257000_2026.01.12.25343268v2.65","doi-asserted-by":"publisher","DOI":"10.1378\/chest.10-2885"},{"key":"2026081710401257000_2026.01.12.25343268v2.66","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-021-00338-8"},{"key":"2026081710401257000_2026.01.12.25343268v2.67","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01450-2"},{"key":"2026081710401257000_2026.01.12.25343268v2.68","doi-asserted-by":"publisher","DOI":"10.1007\/s11748-020-01432-0"},{"key":"2026081710401257000_2026.01.12.25343268v2.69","unstructured":"Karamustafaoglu YA , Yoruk Y , Yanik F , Sarikaya A . Sentinel lymph node mapping in patients with operable non-small cell lung cancer."},{"key":"2026081710401257000_2026.01.12.25343268v2.70","doi-asserted-by":"publisher","DOI":"10.22038\/aojnmb.2019.13195"},{"key":"2026081710401257000_2026.01.12.25343268v2.71","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-11-43"},{"key":"2026081710401257000_2026.01.12.25343268v2.72","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23629-3"},{"key":"2026081710401257000_2026.01.12.25343268v2.73","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2023.09.006"},{"key":"2026081710401257000_2026.01.12.25343268v2.74","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2021.104296"},{"key":"2026081710401257000_2026.01.12.25343268v2.75","unstructured":"Wei J , Li D , Long H , Han M . Immune microenvironment of tumor-draining lymph nodes: insights for immunotherapy. Frontiers in Immunology."},{"key":"2026081710401257000_2026.01.12.25343268v2.76","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-020-02792-5"},{"key":"2026081710401257000_2026.01.12.25343268v2.77","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2019.01.025"},{"key":"2026081710401257000_2026.01.12.25343268v2.78","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-007-0412-0"},{"key":"2026081710401257000_2026.01.12.25343268v2.79","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2004.06.081"},{"key":"2026081710401257000_2026.01.12.25343268v2.80","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e318158d471"},{"key":"2026081710401257000_2026.01.12.25343268v2.81","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcts.2004.03.001"},{"key":"2026081710401257000_2026.01.12.25343268v2.82","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2965"},{"key":"2026081710401257000_2026.01.12.25343268v2.83","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2021.06.006"},{"key":"2026081710401257000_2026.01.12.25343268v2.84","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1998.tb01447.x"},{"key":"2026081710401257000_2026.01.12.25343268v2.85","unstructured":"Rossi D , Berra E , Cerri M , et al. Aberrant somatic hypermutation in transformation of follicular lymphoma and chronic lymphocytic leukemia to diffuse large B-cell lymphoma."},{"key":"2026081710401257000_2026.01.12.25343268v2.86","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1300"},{"key":"2026081710401257000_2026.01.12.25343268v2.87","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1946"},{"key":"2026081710401257000_2026.01.12.25343268v2.88","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01503-3"},{"key":"2026081710401257000_2026.01.12.25343268v2.89","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0672-y"},{"key":"2026081710401257000_2026.01.12.25343268v2.90","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.952220"},{"key":"2026081710401257000_2026.01.12.25343268v2.91","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-014-0052-1"},{"key":"2026081710401257000_2026.01.12.25343268v2.92","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.02.007"},{"key":"2026081710401257000_2026.01.12.25343268v2.93","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2036"},{"key":"2026081710401257000_2026.01.12.25343268v2.94","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.01.013"},{"key":"2026081710401257000_2026.01.12.25343268v2.95","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30138"},{"key":"2026081710401257000_2026.01.12.25343268v2.96","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-016-0232-0"},{"key":"2026081710401257000_2026.01.12.25343268v2.97","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01209"},{"key":"2026081710401257000_2026.01.12.25343268v2.98","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-1481"},{"key":"2026081710401257000_2026.01.12.25343268v2.99","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1658"},{"key":"2026081710401257000_2026.01.12.25343268v2.100","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.17375"},{"key":"2026081710401257000_2026.01.12.25343268v2.101","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.01.004"},{"key":"2026081710401257000_2026.01.12.25343268v2.102","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02208-3"},{"key":"2026081710401257000_2026.01.12.25343268v2.103","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14979"},{"key":"2026081710401257000_2026.01.12.25343268v2.104","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00670-9"},{"key":"2026081710401257000_2026.01.12.25343268v2.105","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10132872"},{"key":"2026081710401257000_2026.01.12.25343268v2.106","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00490-y"},{"key":"2026081710401257000_2026.01.12.25343268v2.107","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.79521"},{"key":"2026081710401257000_2026.01.12.25343268v2.108","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197602)37:2&lt;697::AID-CNCR2820370214&gt;3.0.CO;2-I"},{"key":"2026081710401257000_2026.01.12.25343268v2.109","unstructured":"Beaney A . GSK\u2019s anti-TIM-3 antibody fails in Phase III NSCLC trial. Clinical Trials Arena. July 31, 2025. Accessed September 29, 2025. https:\/\/www.clinicaltrialsarena.com\/news\/gsk-anti-tim-3-antibody-fails-in-phase-iii-nsclc-trial\/"},{"key":"2026081710401257000_2026.01.12.25343268v2.110","doi-asserted-by":"publisher","DOI":"10.36401\/JIPO-23-4"},{"key":"2026081710401257000_2026.01.12.25343268v2.111","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyaf144"},{"key":"2026081710401257000_2026.01.12.25343268v2.112","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-023-01499-1"},{"key":"2026081710401257000_2026.01.12.25343268v2.113","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.01.010"},{"key":"2026081710401257000_2026.01.12.25343268v2.114","unstructured":"Research C for DE and. FDA approves neoadjuvant\/adjuvant nivolumab for resectable non-small cell lung cancer. FDA. Published online October 3, 2024. Accessed May 8, 2026. https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-neoadjuvantadjuvant-nivolumab-resectable-non-small-cell-lung-cancer"},{"key":"2026081710401257000_2026.01.12.25343268v2.115","unstructured":"Research C for DE and. FDA approves neoadjuvant\/adjuvant durvalumab for resectable non-small cell lung cancer. FDA. Published online August 15, 2024. Accessed May 8, 2026. https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-neoadjuvantadjuvant-durvalumab-resectable-non-small-cell-lung-cancer"},{"key":"2026081710401257000_2026.01.12.25343268v2.116","unstructured":"Research C for DE and. FDA approves neoadjuvant\/ adjuvant pembrolizumab for resectable non-small cell lung cancer. FDA. Published online August 9, 2024. Accessed April 9, 2026. https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-neoadjuvant-adjuvant-pembrolizumab-resectable-non-small-cell-lung-cancer"},{"key":"2026081710401257000_2026.01.12.25343268v2.117","unstructured":"Research C for DE and. FDA approves atezolizumab as adjuvant treatment for non-small cell lung cancer. FDA. Published online August 9, 2024. Accessed May 8, 2026. https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-atezolizumab-adjuvant-treatment-non-small-cell-lung-cancer"},{"key":"2026081710401257000_2026.01.12.25343268v2.118","unstructured":"American College of Surgeons. Commission on Cancer. Optimal Resources for Cancer Care: 2020 Standards. Updated December 2024. American College of Surgeons; 2019. https:\/\/www.facs.org\/cancer"},{"key":"2026081710401257000_2026.01.12.25343268v2.119","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"2026081710401257000_2026.01.12.25343268v2.120","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1032"},{"key":"2026081710401257000_2026.01.12.25343268v2.121","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29212-9"},{"key":"2026081710401257000_2026.01.12.25343268v2.122","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-020-1950-6"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.01.12.25343268","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T17:40:22Z","timestamp":1786988422000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.01.12.25343268"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,18]]},"references-count":122,"URL":"https:\/\/doi.org\/10.64898\/2026.01.12.25343268","relation":{},"subject":[],"published":{"date-parts":[[2026,1,18]]},"subtype":"preprint"}}