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. 2021 Sep 9;9:730240. doi: 10.3389/fcell.2021.730240

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Copyright © 2021 Lu, Jin, Du, Hu, Wei, Wang, Li and Li.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Mechanisms of action of lenvatinib in combination with ICB. Lenvatinib promoted the number and function of CD8⁺ T cells and inhibited the number and function of Tregs and Macrophages M2; Lenvatinib enhanced the cytotoxicity of NK cells; Lenvatinib decreased the expression of PD-1, CTLA-4, and TIM3 in T cells and inhibited the exhaustion of T cells; Lenvatinib also inhibits tumor angiogenesis and abnormalities by inhibiting the secretion of angiogenic factors, such as VEGF, FGF, and PDGF, etc. Finally, PD-1/PD-L1 Ab restores the exhausted T cell activity to kill the cancer cell. Therefore, this combination has a synergistic anti-tumor effect.