biostudies-literatureMei ZResearch Project of Jinan Microecological Biomedicine Shandong LaboratoryUnit Project of Chinese Academy of Medical Sciencethe Health Commission of Zhejiang Province1284-1296https://www.ebi.ac.uk/biostudies/studies/S-EPMC10067412biostudies-literatureUnknown114(4)Lenvatinib is the favorable treatment for advanced hepatocellular carcinoma (HCC), and it is currently undergoing phase III clinical trials. However, the specific effects of lenvatinib on PD1⁺ CD8⁺ T cells in HCC microenvironment have not been systematically studied. Here, we established an orthotopic hepa1-6 mouse model treated with lenvatinib to investigate CD8⁺ T cells' role in the tumor and spleen. We found an increasing proportion of TCF-1⁺ in PD1⁺ CD8⁺ T cells and proliferation of PD1⁺ CD8⁺ T cells after lenvatinib treatment. Meanwhile, lenvatinib treatment upregulated the expression of granzyme B on PD1⁺ CD8⁺ T cells both in vitro and in vivo. Lenvatinib activated the endogeCancer scienceLenvatinib enhances antitumor immunity by promoting the infiltration of TCF1⁺ CD8⁺ T cells in HCC via blocking VEGFR2.PMC10067412JBZX-202004JNL-2022008B2019-I2M-5-030JNL-2022002AXu KZhou LQian JPan CWu QWang SMei ZZhen SGao XXu ZfalseLenvatinib enhances antitumor immunity by promoting the infiltration of TCF1⁺ CD8⁺ T cells in HCC via blocking VEGFR2.Lenvatinib is the favorable treatment for advanced hepatocellular carcinoma (HCC), and it is currently undergoing phase III clinical trials. However, the specific effects of lenvatinib on PD1⁺ CD8⁺ T cells in HCC microenvironment have not been systematically studied. Here, we established an orthotopic hepa1-6 mouse model treated with lenvatinib to investigate CD8⁺ T cells' role in the tumor and spleen. We found an increasing proportion of TCF-1⁺ in PD1⁺ CD8⁺ T cells and proliferation of PD1⁺ CD8⁺ T cells after lenvatinib treatment. Meanwhile, lenvatinib treatment upregulated the expression of granzyme B on PD1⁺ CD8⁺ T cells both in vitro and in vivo. Lenvatinib activated the endoge2023-01-01T00:00:00Z2023 Apr2025-04-04T10:42:35.637Z2025-04-04T10:42:35.637ZS-EPMC100674123660999710.1111/cas.15719