{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:53:57Z","timestamp":1785405237897,"version":"3.56.0"},"posted":{"date-parts":[[2025,5,6]]},"group-title":"Immunology","reference-count":65,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}]},{"award":["Cycle for Survival-Equinox Innovation Grant"],"award-info":[{"award-number":["Cycle for Survival-Equinox Innovation Grant"]}],"id":[{"id":"https:\/\/ror.org\/02yrq0923","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Clinical Investigator Award"],"award-info":[{"award-number":["Clinical Investigator Award"]}],"id":[{"id":"https:\/\/ror.org\/01gd7b947","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol Meyers Squibb","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The gastric mucosa is characterized by continuous innate immune surveillance and inflammatory signaling, yet a high proportion of gastric carcinomas (GCs) are recalcitrant to immune-directed therapies. The mechanisms by which GCs evade adaptive immune surveillance within the highly antigenic microenvironment of the gastric mucosa remains unknown. To address this, we collected patient-matched tumor tissue, distant normal tissue, metastasis, and draining lymph nodes to generate a large-scale single-cell immune profiling dataset from 64 patients (n=179 samples, &gt;150,000 cells). From single cell analysis, we identified two distinct sources of impaired tumor surveillance within tumor draining lymph nodes. First, we observed that a significant fraction of tumor draining lymph nodes had undergone cytokine-driven reprogramming, leading to reduced dendritic cell homing and limited T cell priming. Second, T cells undergoing successful activation exhibited limited expansion and constrained differentiation, marked by expression of the quiescence-associated transcription factor Kruppel-like Factor 2 (\n                  <jats:italic>KLF2<\/jats:italic>\n                  ). Overexpression of\n                  <jats:italic>KLF2<\/jats:italic>\n                  in primary T cells limited both their differentiation and cytotoxic capacity. These findings implicate both impaired T cell priming and\n                  <jats:italic>KLF2<\/jats:italic>\n                  -dependent T cell quiescence in limiting T cell immunity in gastric adenocarcinoma. We suggest these findings represent an emerging model for immune silencing in tumors developing from tissues with chronic inflammation.\n                <\/jats:p>","DOI":"10.1101\/2025.05.05.651897","type":"posted-content","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T14:30:16Z","timestamp":1746541816000},"source":"Crossref","is-referenced-by-count":0,"title":["Disrupted priming within draining lymph nodes drives immune quiescence in gastric cancer"],"prefix":"10.64898","author":[{"given":"Sohrab","family":"Salehi","sequence":"first","affiliation":[{"name":"The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily E.","family":"Stroobant","sequence":"additional","affiliation":[{"name":"Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Lees","sequence":"additional","affiliation":[{"name":"The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hui","family":"Lin","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoji","family":"Shimada","sequence":"additional","affiliation":[{"name":"Digestive Disease Center, Showa University, Northern Yokohama Hospital, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miseker","family":"Abate","sequence":"additional","affiliation":[{"name":"Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Department of Surgery, New York-Presbyterian Hospital\/Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5235-4116","authenticated-orcid":false,"given":"Matthew J.","family":"Zatzman","sequence":"additional","affiliation":[{"name":"The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9387-103X","authenticated-orcid":false,"given":"Nicholas","family":"Ceglia","sequence":"additional","affiliation":[{"name":"The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel S.","family":"Freeman","sequence":"additional","affiliation":[{"name":"The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Laszkowska","sequence":"additional","affiliation":[{"name":"Gastroenterology, Hepatology, and Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Maron","sequence":"additional","affiliation":[{"name":"Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5654-5101","authenticated-orcid":false,"given":"Andrew","family":"McPherson","sequence":"additional","affiliation":[{"name":"The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Rusk","sequence":"additional","affiliation":[{"name":"The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliyahu","family":"Havasov","sequence":"additional","affiliation":[{"name":"The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harrison","family":"Drebin","sequence":"additional","affiliation":[{"name":"Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Gu","sequence":"additional","affiliation":[{"name":"Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura H.","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelena Y.","family":"Janjigian","sequence":"additional","affiliation":[{"name":"Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan","family":"Soldatov","sequence":"additional","affiliation":[{"name":"The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan","family":"Chaligne","sequence":"additional","affiliation":[{"name":"Single-cell Analytics Innovation Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohrab P.","family":"Shah","sequence":"additional","affiliation":[{"name":"The Halvorsen Center for Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Computational Oncology, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian E.","family":"Strong","sequence":"additional","affiliation":[{"name":"Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Department of Surgery, New York-Presbyterian Hospital\/Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3100-1298","authenticated-orcid":false,"given":"Santosha A.","family":"Vardhana","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041120443144000_2025.05.05.651897v2.1","unstructured":"SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. <https:\/\/seer.cancer.gov\/statistics-network\/explorer\/> (2025 Apr 16)."},{"key":"2026041120443144000_2025.05.05.651897v2.2","first-page":"1","article-title":"liver flukes and Helicobacter pylori","volume":"61","author":"Schistosomes","year":"1994","journal-title":"IARC Monogr Eval Carcinog Risks Hum"},{"key":"2026041120443144000_2025.05.05.651897v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.01.004"},{"key":"2026041120443144000_2025.05.05.651897v2.4","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-37-2-338"},{"key":"2026041120443144000_2025.05.05.651897v2.5","first-page":"2991","article-title":"Presence of Streptococcus anginosus DNA in esophageal cancer, dysplasia of esophagus, and gastric cancer","volume":"58","year":"1998","journal-title":"Cancer Res"},{"key":"2026041120443144000_2025.05.05.651897v2.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM195506302522601"},{"key":"2026041120443144000_2025.05.05.651897v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.12.033"},{"key":"2026041120443144000_2025.05.05.651897v2.8","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-23-0563"},{"key":"2026041120443144000_2025.05.05.651897v2.9","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4380"},{"key":"2026041120443144000_2025.05.05.651897v2.10","doi-asserted-by":"publisher","DOI":"10.1111\/apm.1965.64.1.31"},{"key":"2026041120443144000_2025.05.05.651897v2.11","doi-asserted-by":"publisher","DOI":"10.1038\/nature13480"},{"key":"2026041120443144000_2025.05.05.651897v2.12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1613683"},{"key":"2026041120443144000_2025.05.05.651897v2.13","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1252"},{"key":"2026041120443144000_2025.05.05.651897v2.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06816-9"},{"key":"2026041120443144000_2025.05.05.651897v2.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"2026041120443144000_2025.05.05.651897v2.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-024-01045-4"},{"key":"2026041120443144000_2025.05.05.651897v2.17","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-021-09624-5"},{"key":"2026041120443144000_2025.05.05.651897v2.18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.140.7.2171"},{"key":"2026041120443144000_2025.05.05.651897v2.19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.140.5.1435"},{"key":"2026041120443144000_2025.05.05.651897v2.20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.144.2.532"},{"key":"2026041120443144000_2025.05.05.651897v2.21","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830170715"},{"key":"2026041120443144000_2025.05.05.651897v2.22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.149.11.3753"},{"key":"2026041120443144000_2025.05.05.651897v2.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5334.1986"},{"key":"2026041120443144000_2025.05.05.651897v2.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-00927-2"},{"key":"2026041120443144000_2025.05.05.651897v2.25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.7.3662"},{"key":"2026041120443144000_2025.05.05.651897v2.26","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4401"},{"key":"2026041120443144000_2025.05.05.651897v2.27","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20221288"},{"key":"2026041120443144000_2025.05.05.651897v2.28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1309378110"},{"key":"2026041120443144000_2025.05.05.651897v2.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.007"},{"key":"2026041120443144000_2025.05.05.651897v2.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.11.021"},{"key":"2026041120443144000_2025.05.05.651897v2.31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2014553118"},{"key":"2026041120443144000_2025.05.05.651897v2.32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1201453109"},{"key":"2026041120443144000_2025.05.05.651897v2.33","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.5.2776"},{"key":"2026041120443144000_2025.05.05.651897v2.34","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-09-3605"},{"key":"2026041120443144000_2025.05.05.651897v2.35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004420"},{"key":"2026041120443144000_2025.05.05.651897v2.36","doi-asserted-by":"publisher","DOI":"10.1172\/JCI77993"},{"key":"2026041120443144000_2025.05.05.651897v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/nature07657"},{"key":"2026041120443144000_2025.05.05.651897v2.38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201954"},{"key":"2026041120443144000_2025.05.05.651897v2.39","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.126"},{"key":"2026041120443144000_2025.05.05.651897v2.40","doi-asserted-by":"publisher","DOI":"10.1126\/science.adn2337"},{"key":"2026041120443144000_2025.05.05.651897v2.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113323"},{"key":"2026041120443144000_2025.05.05.651897v2.42","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.380"},{"key":"2026041120443144000_2025.05.05.651897v2.43","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4333"},{"key":"2026041120443144000_2025.05.05.651897v2.44","unstructured":"Amin, M. , Edge, S. , Greene, F. &, et al. AJCC Cancer Staging Manual. 8th edn, (Springer, 2017)."},{"key":"2026041120443144000_2025.05.05.651897v2.45","doi-asserted-by":"publisher","DOI":"10.1111\/apm.1965.64.1.31"},{"key":"2026041120443144000_2025.05.05.651897v2.46","doi-asserted-by":"publisher","DOI":"10.1038\/nature13480"},{"key":"2026041120443144000_2025.05.05.651897v2.47","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4333"},{"key":"2026041120443144000_2025.05.05.651897v2.48","unstructured":"NCCN\u00ae. NCCN Guidelines\u00ae Gastric Cancer 2.2023, <https:\/\/www.nccn.org\/guidelines\/guidelines-detail?category=1&id=1434> (2023)."},{"key":"2026041120443144000_2025.05.05.651897v2.49","doi-asserted-by":"publisher","DOI":"10.1002\/jso.24226"},{"key":"2026041120443144000_2025.05.05.651897v2.50","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1603-1"},{"key":"2026041120443144000_2025.05.05.651897v2.51","doi-asserted-by":"publisher","DOI":"10.1101\/gr.254557.119"},{"key":"2026041120443144000_2025.05.05.651897v2.52","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.73600.2"},{"key":"2026041120443144000_2025.05.05.651897v2.53","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0"},{"key":"2026041120443144000_2025.05.05.651897v2.54","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"2026041120443144000_2025.05.05.651897v2.55","doi-asserted-by":"publisher","DOI":"10.48550\/arxiv.1802.03426"},{"key":"2026041120443144000_2025.05.05.651897v2.56","doi-asserted-by":"publisher","DOI":"10.1145\/2783258.2783414"},{"key":"2026041120443144000_2025.05.05.651897v2.57","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06816-9"},{"key":"2026041120443144000_2025.05.05.651897v2.58","unstructured":"Salehi, S. , Nazaret, A. , Shah, S. P. & Blei, D. M . Population Priors for Matrix Factorization. Transactions on Machine Learning Research (2024)."},{"key":"2026041120443144000_2025.05.05.651897v2.59","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2017.1285773"},{"key":"2026041120443144000_2025.05.05.651897v2.60","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"2026041120443144000_2025.05.05.651897v2.61","doi-asserted-by":"publisher","DOI":"10.1007\/bf01587094"},{"key":"2026041120443144000_2025.05.05.651897v2.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.01.029"},{"key":"2026041120443144000_2025.05.05.651897v2.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.08.029"},{"key":"2026041120443144000_2025.05.05.651897v2.64","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-00927-2"},{"key":"2026041120443144000_2025.05.05.651897v2.65","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1059"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.05.05.651897","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T03:44:41Z","timestamp":1775965481000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.05.05.651897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":65,"URL":"https:\/\/doi.org\/10.1101\/2025.05.05.651897","relation":{},"subject":[],"published":{"date-parts":[[2025,5,6]]},"subtype":"preprint"}}