# Spleen-targeted neoantigen mRNA vaccine induces ISG15<sup>+</sup> CD8<sup>+</sup> T cell-mediated tertiary lymphoid structure formation in hepatocellular carcinoma

Article · 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

- Archive id: doi:10.1016/j.xcrm.2026.102754
- Published: 2026-04-20
- Venue: Cell reports. Medicine
- DOI: https://doi.org/10.1016/j.xcrm.2026.102754
- PMID: 42013842
- PMCID: PMC13198314
- Citations: 1
- Source URL: https://doi.org/10.1016/j.xcrm.2026.102754
- PDF: https://europepmc.org/articles/PMC13198314/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [mRNA Therapeutics & Cancer Vaccines](https://space-kitty.com/topics/mrna-cancer-vaccines)

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