{"id":"doi:10.1016/j.xcrm.2026.102754","kind":"article","title":"Spleen-targeted neoantigen mRNA vaccine induces ISG15<sup>+</sup> CD8<sup>+</sup> T cell-mediated tertiary lymphoid structure formation in hepatocellular carcinoma","authors":["Lin X","Chen G","Tang R","Wu M","Zhang D","Lin F","Guan J","Yang J","Dong X","Zheng X","Qiu L","Yu H","Cai Z","Liu X"],"author_count":14,"year":2026,"published":"2026-04-20","venue":"Cell reports. Medicine","cited_by":1,"doi":"10.1016/j.xcrm.2026.102754","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.xcrm.2026.102754","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.xcrm.2026.102754","updated":null,"pmid":"42013842","pmcid":"PMC13198314","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13198314/pdf","abstract":"The efficacy of neoantigen vaccine for advanced hepatocellular carcinoma (HCC) is limited largely due to insufficient T cell mobilization and activation. Herein, we develop a spleen-targeted neoantigen mRNA vaccine (STNvac) with highly efficient spleen-selective mRNA transfection. Using a three-dose vaccination regimen, STNvac demonstrates remarkable therapeutic efficacy in orthotopic HCC model with a high likelihood of complete tumor regression and significantly improved survival rates (p < 0.0001). Notably, we identify a distinct ISG15 + CD8 + T cell population as crucial mediators of STNvac-induced immunity with potent antigen-processing and cytotoxic capacities. Intriguingly, STNvac promotes the formation of tertiary lymphoid structures (TLSs) through GZMA-F2R-mediated interactions between ISG15 + CD8 + T cells and antigen-presenting cells (APCs), which is also confirmed in HCC patients. Taken together, our findings demonstrate the potent antitumor efficacy of spleen-targeted mRNA vaccine and reveal its underlying immune cell interactive mechanisms, presenting high potential for clinical translation.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Spleen-targeted neoantigen mRNA vaccine induces ISG15<sup>+</sup> CD8<sup>+</sup> T cell-mediated tertiary lymphoid structure formation in hepatocellular carcinoma\" by Lin X, Chen G, Tang R et al., https://doi.org/10.1016/j.xcrm.2026.102754, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"mrna-cancer-vaccines","name":"mRNA Therapeutics & Cancer Vaccines","domain_slug":"medicine"}],"cited_in_dossiers":[]}