{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:54:46Z","timestamp":1781585686855,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102021R1A5A2030333"],"award-info":[{"award-number":["NRF\u20102021R1A5A2030333"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The infiltration and cytotoxicity of T lymphocytes are critical for cancer immunotherapy efficacy; however, the behavior of these immune cells has not been thoroughly investigated. Herein, a Tumor\u2010Immune\u2010On\u2010Chip is established using cells acquired from the tissues of a patient with colorectal cancer to monitor T lymphocytes. Through the Tumor\u2010Immune\u2010On\u2010Chip, the interaction between tumor spheroid and either T lymphocytes expanded from tumors (tumor\u2010infiltrating lymphocytes; TILs) or lymph nodes (lymph node\u2010derived lymphocytes; LN T cells) are investigated. Although initial 24\u2010h analysis showed no statistical differences, extended 48\u2010h observation revealed a significant deviation in T cell\u2010mediated cell death signals between TILs and LN T cells. TILs demonstrated more potent cytotoxic effects than LN T cells after 48\u2009h. The number of tumor\u2010infiltrating CD3\n                    <jats:sup>+<\/jats:sup>\n                    cells and cleaved caspase\u20103 expression levels were 4\u2010 and 2.1\u2010fold higher, respectively, in TIL co\u2010cultures compared to LN T cell co\u2010cultures. Therefore, this proof\u2010of\u2010concept platform allows us to explore the patient\u2010specific tumor\u2010immune microenvironment, focusing on different types of T lymphocytes and establishing methodology for future clinical applications.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrial.gov\">ClinicalTrial.gov<\/jats:ext-link>\n                    identifier: NCT02589496\n                  <\/jats:p>","DOI":"10.1002\/cam4.71906","type":"journal-article","created":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T21:02:45Z","timestamp":1777842165000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor\u2010Immune\u2010On\u2010Chip to Evaluate Pathophysiological Feature of T Lymphocytes Expanded from Patient Tumors and Lymph Node Tissues"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8495-7058","authenticated-orcid":false,"given":"Gyu\u2010Bon","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University and Samsung Medical Center  Seoul Republic of Korea"},{"name":"Samsung Medical Center  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun\u2010Joo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University and Samsung Medical Center  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You Jeong","family":"Heo","sequence":"additional","affiliation":[{"name":"Neocella, Inc.  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihoon","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of BioNano Technology Gachon University  Gyeonggi Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won\u2010Suk","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Surgery Gil Medical Center, College of Medicine, Gachon University  Incheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1192-0972","authenticated-orcid":false,"given":"Sujin","family":"Hyung","sequence":"additional","affiliation":[{"name":"Samsung Medical Center  Seoul Republic of Korea"},{"name":"Division of Hematology\u2010Oncology, Department of Medicine Samsung Medical Center, Sungkyunkwan University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0306-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01048-4"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-024-00998-8"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.808964"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.23.7370"},{"key":"e_1_2_10_7_1","first-page":"4155","article-title":"Tumor\u2010Infiltrating Lymphocytes: The Regulator of Melanoma Evolution","volume":"17","author":"Antohe M.","year":"2019","journal-title":"Oncology Letters"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.03.013"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129139"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0218-0"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3245"},{"key":"e_1_2_10_12_1","first-page":"910","article-title":"2D and 3D Cell Cultures\u2014A Comparison of Different Types of Cancer Cell Cultures","volume":"14","author":"Kapa\u0142czy\u0144ska M.","year":"2018","journal-title":"Archives of Medical Science"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-022-00887-3"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-022-01280-0"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52253"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2214569119"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b00686"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1LC00182E"},{"key":"e_1_2_10_19_1","article-title":"Microfluidic Platforms for Studying Tumor\u2013Immune Interactions","volume":"12","author":"Song J.","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc2331"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.3c02995"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu191"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020177"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00565-9"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1347181"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-021-02006-4"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2017.25"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.690499"},{"key":"e_1_2_10_29_1","article-title":"Adoptive Transfer of Tumor\u2010Infiltrating Lymphocytes in Melanoma: A Phase I\/II Study","volume":"8","author":"Berg J. 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