The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma

作者：Jie Zhu, Peiqi Fang, Chong Wang, Meixiu Gu, Baishen Pan, Wei Guo, Xinrong Yang, Beili Wang · 发表于：Cancer Medicine · 年份：2021 · DOI：10.1002/cam4.4312 · 被引用次数：33 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Fibroblast Growth Factor Research、Cancer Immunotherapy and Biomarkers

BACKGROUND: Lenvatinib is a novel multiple receptor tyrosine kinase inhibitor used for hepatocellular carcinoma (HCC) treatment. Although its main function is to suppress VEGFR and FGFR pathway, its immunomodulatory activity in HCC is not elucidated. Thus, this study aimed to investigate the immunomodulatory capability of lenvatinib in HCC. MATERIAL AND METHODS: Totally 47 patients with HCC were enrolled in this study, and the immune cells and serum cytokine profiles before initiation of treatment and after 1 and 3 months were measured. The immune checkpoint receptors on the immune cells were also evaluated. Kaplan-Meier survival estimate and log rank tests were used to assess the prognostic value. RESULT: The frequency of T helper (Th) cells and T regulatory (Treg) cells reduced after lenvatinib treatment, while cytotoxic T lymphocyte (CTL) cells increased significantly. The cytokine profiles showed IL-2, IL-5, IFN-γ increased; other cytokines including IL-6, IL-10, TNF- α and TNF- β decreased with lenvatinib therapy. Furthermore, the PD-1 and TIM-3 expressed on CTL had greatly decreased; the expression of TIM-3 and CTLA-4 was reduced on Treg cells as well. Besides, the new index CTL/Treg ratio was created, and low ratio was associated with the unfavorable outcome of HCC patients. CONCLUSION: Our results confirmed that lenvatinib is capable of improving patients' immune status, saving the effector cells from exhaustion status and inhibiting the number and function of immunos...