{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T18:46:24Z","timestamp":1782758784047,"version":"3.54.5"},"reference-count":42,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) funded by the Korea government","award":["NRF-2022R1A2C3007292"],"award-info":[{"award-number":["NRF-2022R1A2C3007292"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>IL-7 is a critical cytokine in T cell development, survival, and homeostasis. Previous preclinical and clinical studies reported that IL-7 treatment increased T cell counts, but its effect on peripheral blood T cells in cancer patients and molecular mechanisms have not been explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We investigated effects of long-acting recombinant human IL-7 conjugated to a hybrid IgD\/IgG4 Fc domain (rhIL-7-hyFc) on peripheral T cells in patients with advanced solid tumors. Peripheral blood samples were collected before and after treatment, followed by analysis through single-cell transcriptomics and flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We found that rhIL-7-hyFc induced marked expansion of proliferating T cells, and promoted transcriptional changes associated with immune activation, cell cycle progression, and antiapoptosis. Trajectory analysis revealed that posttreatment T cells had distinct transcriptional states enriched for cytokine- and TCR-mediated signaling pathways. Notably, a second dose administered after 3 weeks yielded diminished proliferation and minimal transcriptional changes, which were independent of antidrug antibody or CD127 downmodulation. Examination of elements of the IL-7 signaling pathway revealed intact proximal signaling (e.g., STAT5 phosphorylation) but downregulation of distal elements, including PIM-1 kinase and c-Myc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Our results demonstrate that rhIL-7-hyFc induces robust peripheral T cell expansion and activation in patients with solid tumors, supporting its potential use for lymphopenic patients treated with cancer immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT03478995 and NCT03619239.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>National Research Foundation of Korea (NRF-2022R1A2C3007292 and RS-2024-00439160), Ministry of Food and Drug Safety (RS-2025-02213409), and the Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute (RS-2025-25460003).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.203629","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:00:37Z","timestamp":1776787237000},"source":"Crossref","is-referenced-by-count":0,"title":["Long-acting IL-7 induces distinct transcriptomic features in peripheral T cells of patients with solid tumors"],"prefix":"10.1172","volume":"11","author":[{"given":"Hocheol","family":"Jang","sequence":"first","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sojeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heewon","family":"Kim","sequence":"additional","affiliation":[{"name":"Genexine, Inc., Seoul, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Sun","family":"Byun","sequence":"additional","affiliation":[{"name":"Genexine, Inc., Seoul, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myung Ah","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University, Seoul, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Hee","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do-Hyun","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin-Soo","family":"Jeun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo Hyuk","family":"Sohn","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6363-7736","authenticated-orcid":true,"given":"Su-Hyung","family":"Park","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6308-9503","authenticated-orcid":true,"given":"Eui-Cheol","family":"Shin","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.09.005"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01630-x"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-023-00521-2"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0549-5"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.clbc.2012.04.004"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23217"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.050138"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0395-x"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-3845"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2018.01.003"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0479-x"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2022.156049"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.10.2983"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2012.04.010"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxm102"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nri2970"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4110\/in.2024.24.e9"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2020.12.004"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.98960"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38052"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-186601"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.16485"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-1303"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939271"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-0947"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-024-02617-7"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101567"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021006591"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12800"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-025-03069-3"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-0195"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-212852"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1618"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102536"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15133490"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-042020-042741"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2019.1581547"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01522-4"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3892\/mco.2020.2157"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0383-1"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.778830"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2018021063"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/203629\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T18:26:00Z","timestamp":1782757560000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/203629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,4,23]]},"published-print":{"date-parts":[[2026,6,8]]}},"alternative-id":["10.1172\/jci.insight.203629"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.203629","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]},"article-number":"e203629"}}