| Autor: |
Mei, Zhibin, Gao, Xingxing, Pan, Caixu, Wu, Qinchuan, Wang, Shuai, Qian, Junjie, Xu, Zhentian, Xu, Kangdi, Zhou, Lin, Zhen, Shushen |
| Zdroj: |
Cancer Science; Apr2023, Vol. 114 Issue 4, p1284-1296, 13p |
| Abstrakt: |
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 endogenous mTOR pathway of exhausted CD8+ T cells, and mTOR pathway blockade eliminated the antitumor effect of lenvatinib and function of PD1+ CD8+ T cells. The effects of the mTOR pathway on PD1+ CD8+ T cells after lenvatinib treatment were mediated by VEGFR2 inhibition. Overall, our work provides insight into the mechanism of lenvatinib's antitumor efficacy through exhausted CD8+ T cells in HCC treatment. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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