{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:28:26Z","timestamp":1792787306462,"version":"4.5.0"},"reference-count":38,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"unspecified","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Chongqing Science and Health Joint Medical High-end Talent Project","award":["2022GDRC012"],"award-info":[{"award-number":["2022GDRC012"]}]},{"name":"Science and Technology Research Program of Chongqing Municipal Education Commission","award":["KJZD-K202100402"],"award-info":[{"award-number":["KJZD-K202100402"]}],"id":[{"id":"https:\/\/ror.org\/031nm5713","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The first affiliated hospital of Chongqing medical university Full-time Post-Doctoral Research Startup Fund","award":["0303020201P0576"],"award-info":[{"award-number":["0303020201P0576"]}],"id":[{"id":"https:\/\/ror.org\/033vnzz93","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Chongqing Biomedical R&D Major Special Project","award":["CSTB2022TIAD-STX0013"],"award-info":[{"award-number":["CSTB2022TIAD-STX0013"]}]},{"name":"Natural Science Foundation of Chongqing China","award":["2023NSCQ-LZX0104"],"award-info":[{"award-number":["2023NSCQ-LZX0104"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,9,21]]},"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Interleukin-7 receptor (IL7R) signaling is critical for T-cell survival, homeostasis, and immune function, but the therapeutic potential of increasing IL7R expression through messenger RNA (mRNA) delivery remains poorly defined. We investigated whether IL7R mRNA therapy could enhance antitumor immunity and improve tumor control in preclinical cancer models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>IL7R mRNA formulated in lipid nanoparticles (LNPs) was administered by combined intratumoral and intravenous injection in syngeneic B16 melanoma and Lewis lung carcinoma (LLC) models, with empty LNPs included as vehicle controls. Therapeutic efficacy, IL7R expression, immune responses, transcriptomic remodeling, T-cell receptor (TCR) repertoire changes, and treatment tolerability were evaluated using complementary molecular, immunological, and sequencing approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IL7R mRNA treatment increased IL7R transcript and protein levels in tumor-bearing mice, whereas empty LNPs did not produce comparable increases. Treatment increased tumor-infiltrating CD8 T-cell frequencies, suppressed tumor growth and prolonged survival in both B16 and LLC models; empty LNP controls did not reproduce the therapeutic effect. Cytokine and transcriptomic analyses showed treatment-associated activation of inflammatory, T-cell, interferon, and antigen-receptor signaling programs. TCR sequencing further demonstrated increased repertoire diversity and reduced clonal dominance following IL7R mRNA treatment. No obvious body-weight loss or marked changes in serum alanine aminotransferase, aspartate aminotransferase, or creatinine were observed under the tested conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>IL7R mRNA therapy increases IL7R expression and is associated with enhanced T-cell antitumor responses, tumor growth suppression, improved survival, and remodeling of the tumor immune environment. These findings support further mechanistic and preclinical evaluation of IL7R mRNA-based cancer immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2026-017160","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:00:27Z","timestamp":1791385227000},"page":"e017160","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["IL7R mRNA therapy enhances antitumor T cell immunity and suppresses tumor growth in preclinical tumor models"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4800-5762","authenticated-orcid":false,"given":"Adeel ur","family":"Rehman","sequence":"first","affiliation":[{"name":"Clinical Molecular Medicine Testing Center, Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, China"},{"name":"Western Institute of Digital-Intelligent Medicine, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0344-7579","authenticated-orcid":false,"given":"Muhammad Naveed","family":"Khan","sequence":"additional","affiliation":[{"name":"Clinical Molecular Medicine Testing Center, Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, China"},{"name":"Western Institute of Digital-Intelligent Medicine, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5089-4019","authenticated-orcid":false,"given":"Aleena","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Western Institute of Digital-Intelligent Medicine, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8340-389X","authenticated-orcid":false,"given":"Qianshan","family":"Qin","sequence":"additional","affiliation":[{"name":"Suzhou Abogen Biosciences, Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2242-6503","authenticated-orcid":false,"given":"Xiaojing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Suzhou Abogen Biosciences, Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3183-3797","authenticated-orcid":false,"given":"Muhammad Arif","family":"Asghar","sequence":"additional","affiliation":[{"name":"Clinical Molecular Medicine Testing Center, Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, China"},{"name":"Western Institute of Digital-Intelligent Medicine, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3873-0618","authenticated-orcid":false,"given":"Dandan","family":"Ling","sequence":"additional","affiliation":[{"name":"Suzhou Abogen Biosciences, Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7391-2428","authenticated-orcid":false,"given":"Pei","family":"Wang","sequence":"additional","affiliation":[{"name":"Suzhou Abogen Biosciences, Suzhou, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8421-1926","authenticated-orcid":false,"given":"Ying","family":"Luo","sequence":"additional","affiliation":[{"name":"Clinical Molecular Medicine Testing Center, Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, China"},{"name":"Western Institute of Digital-Intelligent Medicine, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7156-3132","authenticated-orcid":false,"given":"Zhihuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thyroid Surgery, Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lexin","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Molecular Medicine Testing Center, Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, China"},{"name":"Western Institute of Digital-Intelligent Medicine, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1035-4895","authenticated-orcid":false,"given":"Hanyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology and Tumor Immunology, Virchow Campus, and Molecular Cancer Research Center, Charit\u00e9\u2011University Medical Center, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5533-7995","authenticated-orcid":false,"given":"Xiaosong","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Molecular Medicine Testing Center, Key Laboratory of Clinical Laboratory Diagnostics (Chinese Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, China"},{"name":"Western Institute of Digital-Intelligent Medicine, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"2026100708002113000_14.10.e017160.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4278"},{"key":"2026100708002113000_14.10.e017160.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature18300"},{"key":"2026100708002113000_14.10.e017160.3","doi-asserted-by":"publisher","DOI":"10.4155\/tde-2016-0006"},{"key":"2026100708002113000_14.10.e017160.4","doi-asserted-by":"crossref","first-page":"112205","DOI":"10.1016\/j.intimp.2024.112205","article-title":"Enhancing antitumor immunity and achieving tumor eradication with IL11RA mRNA immunotherapy","volume":"134","author":"Ur Rehman","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"2026100708002113000_14.10.e017160.5","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/s44222-023-00030-y","article-title":"Engineering cytokine therapeutics","volume":"1","author":"Deckers","year":"2023","journal-title":"Nat Rev Bioeng"},{"key":"2026100708002113000_14.10.e017160.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.11.001"},{"key":"2026100708002113000_14.10.e017160.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.01.001"},{"key":"2026100708002113000_14.10.e017160.8","first-page":"31","article-title":"Self-amplifying mRNA-Based Vaccine Technology and Its Mode of Action","volume":"440","author":"Maruggi","year":"2022","journal-title":"Curr Top Microbiol Immunol"},{"key":"2026100708002113000_14.10.e017160.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.01.020"},{"key":"2026100708002113000_14.10.e017160.10","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abc7804","article-title":"Local delivery of mRNA-encoded cytokines promotes antitumor immunity and tumor eradication across multiple preclinical tumor models","volume":"13","author":"Hotz","year":"2021","journal-title":"Sci Transl Med"},{"key":"2026100708002113000_14.10.e017160.11","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-2867"},{"key":"2026100708002113000_14.10.e017160.12","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aat9143","article-title":"Durable anticancer immunity from intratumoral administration of IL-23, IL-36\u03b3, and OX40L mRNAs","volume":"11","author":"Hewitt","year":"2019","journal-title":"Sci Transl Med"},{"key":"2026100708002113000_14.10.e017160.13","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-024-54877-9","article-title":"Intratumoral delivery of lipid nanoparticle-formulated mRNA encoding IL-21, IL-7, and 4-1BBL induces systemic anti-tumor immunity","volume":"15","author":"Hamouda","year":"2024","journal-title":"Nat Commun"},{"key":"2026100708002113000_14.10.e017160.14","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32020"},{"key":"2026100708002113000_14.10.e017160.15","doi-asserted-by":"publisher","DOI":"10.1097\/01.cji.0000210386.55951.c2"},{"key":"2026100708002113000_14.10.e017160.16","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-21-0947"},{"key":"2026100708002113000_14.10.e017160.17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903151"},{"key":"2026100708002113000_14.10.e017160.18","doi-asserted-by":"crossref","first-page":"104042","DOI":"10.1016\/j.cellimm.2020.104042","article-title":"Dual-target IL-12-containing nanoparticles enhance T cell functions for cancer immunotherapy","volume":"349","author":"Li","year":"2020","journal-title":"Cell Immunol"},{"key":"2026100708002113000_14.10.e017160.19","doi-asserted-by":"crossref","first-page":"168822","DOI":"10.1016\/j.jmb.2024.168822","article-title":"Engineered mRNAs With Stable Structures Minimize Double-stranded RNA Formation and Increase Protein Expression","volume":"436","author":"Qin","year":"2024","journal-title":"J Mol Biol"},{"key":"2026100708002113000_14.10.e017160.20","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2019.1669558"},{"key":"2026100708002113000_14.10.e017160.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.024"},{"key":"2026100708002113000_14.10.e017160.22","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty560"},{"key":"2026100708002113000_14.10.e017160.23","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"2026100708002113000_14.10.e017160.24","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3122"},{"key":"2026100708002113000_14.10.e017160.25","doi-asserted-by":"crossref","unstructured":"Love MI , Huber W , Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 2014;15. doi:10.1186\/s13059-014-0550-8","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026100708002113000_14.10.e017160.26","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab711"},{"key":"2026100708002113000_14.10.e017160.27","doi-asserted-by":"crossref","DOI":"10.1186\/s13073-020-00783-w","article-title":"The murine Microenvironment Cell Population counter method to estimate abundance of tissue-infiltrating immune and stromal cell populations in murine samples using gene expression","volume":"12","author":"Petitprez","year":"2020","journal-title":"Genome Med"},{"key":"2026100708002113000_14.10.e017160.28","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz430"},{"key":"2026100708002113000_14.10.e017160.29","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3364"},{"key":"2026100708002113000_14.10.e017160.30","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1004503","article-title":"VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires","volume":"11","author":"Shugay","year":"2015","journal-title":"PLoS Comput Biol"},{"key":"2026100708002113000_14.10.e017160.31","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1093\/annonc\/mdy423","article-title":"Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT)","volume":"29","author":"Marabelle","year":"2018","journal-title":"Ann Oncol"},{"key":"2026100708002113000_14.10.e017160.32","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2020-001749","article-title":"Therapeutic depletion of CCR8+ tumor-infiltrating regulatory T cells elicits antitumor immunity and synergizes with anti-PD-1 therapy","volume":"9","author":"Van Damme","year":"2021","journal-title":"J Immunother Cancer"},{"key":"2026100708002113000_14.10.e017160.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.02.021"},{"key":"2026100708002113000_14.10.e017160.34","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00232-020-00122-5","article-title":"Identification of Human Secretome and Membrane Proteome-Based Cancer Biomarkers Utilizing Bioinformatics","volume":"253","author":"Rehman","year":"2020","journal-title":"J Membr Biol"},{"key":"2026100708002113000_14.10.e017160.35","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.2463"},{"key":"2026100708002113000_14.10.e017160.36","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1111\/jcmm.17338","article-title":"Systematic molecular analysis of the human secretome and membrane proteome in gastrointestinal adenocarcinomas","volume":"26","author":"Rehman","year":"2022","journal-title":"J Cell Mol Med"},{"key":"2026100708002113000_14.10.e017160.37","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0163"},{"key":"2026100708002113000_14.10.e017160.38","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.ymthe.2018.12.013","article-title":"Self-Amplifying RNA Vaccines for Venezuelan Equine Encephalitis Virus Induce Robust Protective Immunogenicity in Mice","volume":"27","author":"Samsa","year":"2019","journal-title":"Mol Ther"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2026-017160","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:00:31Z","timestamp":1791385231000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2026-017160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":38,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10,7]]},"published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1136\/jitc-2026-017160"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2026-017160","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]}}}