Anlotinib optimizes anti-tumor innate immunity to potentiate the therapeutic effect of PD-1 blockade in lung cancer
Anlotinib optimizes anti-tumor innate immunity to potentiate the therapeutic effect of PD-1 blockade in lung cancer
复制标题
安罗替尼优化抗肿瘤先天免疫，增强PD-1阻断对肺癌的治疗效果
DOI：
10.1007/s00262-020-02641-5
复制
发表时间：
2020-06-23
影响因子：
5.8
通讯作者：
Pan, Zhanyu
中科院分区：
文献类型：
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作者：
Yang, Yinli;Li, Ling;Pan, Zhanyu
背景许多抗血管生成药物具有调节肿瘤微环境和改善免疫治疗的潜力。在三线临床试验中，Anlotinib已证明在非小细胞肺癌（NSCLC）中具有抗肿瘤疗效。然而，其在免疫调节中的作用和潜在的协同抗肿瘤作用与免疫检查点抑制相结合仍不清楚。MethodsHere，基于同系肺癌小鼠模型，肿瘤内免疫变化后，安洛替尼治疗的模型进行了评估。结果Anlotinib可增加天然免疫细胞（包括NK细胞）和抗原呈递细胞（包括M1样肿瘤相关巨噬细胞（TAM）和树突状细胞（DC））的浸润，而M2样TAM的百分比显著降低。随后，当与PD-1/PD-L1（程序性细胞死亡1/PD-1配体1）封锁相结合，安洛替尼赋予显着的协同治疗benefits.ConclusionsOverall，这些研究结果描述了安洛替尼在肿瘤微环境中的先天免疫细胞的作用和潜在的协同抗肿瘤组合与免疫检查点抑制。
BackgroundMany anti-angiogenic agents have the potential to modulate the tumor microenvironment and improve immunotherapy. Anlotinib has demonstrated anti-tumor efficacy in non-small cell lung cancer (NSCLC) in third-line clinical trials. However, its roles in immune regulation and potentially synergistic anti-tumor effect in combination with immune checkpoint inhibition remain unclear.MethodsHere, based on a syngeneic lung cancer mouse model, the intratumoral immunological changes post-anlotinib treatment in the model were assessed. Furthermore, it was tested whether anlotinib could enhance the anti-tumor effect of αPD-1 in vivo.ResultsThis study shows that anlotinib increased infiltration of the innate immune cells, including natural killer (NK) cells, and antigen-presenting cells (APC), which include M1-like tumor-associated macrophages (TAM) and dendritic cells (DC), whereas the percentage of M2-like TAM was dramatically reduced. Subsequently, when combined with PD-1/PD-L1 (programmed cell death 1/PD-1 ligand 1) blockade, anlotinib conferred significantly synergistic therapeutic benefits.ConclusionsOverall, these findings describe a role for anlotinib in the innate immune cells in the tumor microenvironment and a potentially synergistic anti-tumor combination with immune checkpoint inhibition.