Lenvatinib promotes antitumor immunity by enhancing the tumor infiltration and activation of NK cells.
Lenvatinib promotes antitumor immunity by enhancing the tumor infiltration and activation of NK cells.
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仑伐替尼通过增强肿瘤浸润和 NK 细胞活化来促进抗肿瘤免疫。
DOI：
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发表时间：
2019
影响因子：
5.3
通讯作者：
Junnian Zheng
中科院分区：
文献类型：
--
作者：
Qing Zhang;Hongyan Liu;Hanhan Wang;Mengmeng Lu;Yangna Miao;Jiage Ding;Huizhong Li;Xiaoge Gao;Shishuo Sun;Junnian Zheng
根据之前的报道，乐伐替尼的抗癌功效主要归因于其抗血管生成活性和抑制肿瘤增殖的能力，这是通过靶向受体酪氨酸激酶（RTK）介导的。然而，仑伐替尼对肿瘤免疫调节的影响却很少被探索。在这里，我们证明乐伐替尼有效抑制小鼠黑色素瘤和肾癌，并且这种抑制与自然杀伤（NK）细胞增强的肿瘤浸润有关。重要的是，乐伐替尼诱导的肿瘤生长抑制通过抗体介导的 NK 细胞耗竭或用抗 CXCR3 阻断抗体阻断 NK 细胞趋化性而减弱。此外，乐伐替尼还增强了肿瘤浸润 NK 细胞的天然细胞毒性受体（NCR）表达和肿瘤组织中细胞毒性细胞因子的表达。因此，这些数据表明乐伐替尼不仅可以用作对抗肿瘤血管生成和增殖的直接细胞毒性药物，而且可以作为通过增强肿瘤浸润和 NK 细胞活化来增强基于免疫的癌症治疗功效的有效辅助药物。
Based on previous reports, the efficacy of lenvatinib against cancer is mainly attributed to its antiangiogenic activity and its ability to suppress tumor proliferation, which are mediated by targeting receptor tyrosine kinases (RTKs). However, the effects of lenvatinib on tumor immune modulation have rarely been explored. Here, we show that lenvatinib effectively inhibited murine melanoma and renal cancer, and this inhibition was associated with enhanced tumor infiltration by natural killer (NK) cells. Critically, lenvatinib-induced tumor growth inhibition was attenuated by antibody-mediated NK cell depletion or the blockade of NK cell chemotaxis with an anti-CXCR3 blocking antibody. In addition, the expression of natural cytotoxicity receptors (NCRs) by tumor-infiltrating NK cells and the expression of cytotoxic cytokines in the tumor tissue were also augmented by lenvatinib. These data thus suggest that lenvatinib may be used not only as a direct cytotoxic drug against tumor angiogenesis and proliferation but also as a potent adjunct for enhancing the efficacy of immune-based cancer therapies by enhancing the tumor infiltration and activation of NK cells.
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影响因子：
2.1
作者：
Tohyama O;Matsui J;Kodama K;Hata-Sugi N;Kimura T;Okamoto K;Minoshima Y;Iwata M;Funahashi Y
通讯作者：
Funahashi Y
影响因子：
9.7
作者：
Okamoto, Kiyoshi;Kodama, Kotaro;Tsuruoka, Akihiko
通讯作者：
Tsuruoka, Akihiko
影响因子：
2.6
作者：
Matsubara, Nobuaki;Naito, Yoichi;Takahashi, Shunji
通讯作者：
Takahashi, Shunji
影响因子：
6.1
作者：
G. Roviello;S. P. Corona;G. Bozza;M. Aieta;D. Generali;M. Rodriquenz;A. Mileo;M. Imperatori;A. Ianza;R. Conca;N. Sobhani
通讯作者：
G. Roviello;S. P. Corona;G. Bozza;M. Aieta;D. Generali;M. Rodriquenz;A. Mileo;M. Imperatori;A. Ianza;R. Conca;N. Sobhani
影响因子：
4
作者：
Matsuki M;Hoshi T;Yamamoto Y;Ikemori-Kawada M;Minoshima Y;Funahashi Y;Matsui J
通讯作者：
Matsui J