封锁
肺癌
渗透(HVAC)
医学
CD8型
癌症研究
细胞毒性T细胞
癌症治疗
PD-L1
免疫疗法
CCL5
T细胞
药理学
免疫系统
肿瘤科
免疫学
化学
内科学
癌症
白细胞介素2受体
受体
生物化学
材料科学
体外
复合材料
作者
Jie Luo,Kebin Cheng,Xianxiu Ji,Caixia Gao,Ren Zhu,Jiayi Chen,Handong Wang,Qi Huang,Quanbin Xu
出处
期刊:PubMed
日期:2024-04-13
卷期号:: 216892-216892
标识
DOI:10.1016/j.canlet.2024.216892
摘要
Non-small cell lung cancer (NSCLC) is a leading cause of mortality worldwide and requires effective treatment strategies. Recently, the development of a novel multiple-target tyrosine kinase inhibitor, anlotinib, has drawn increasing attention, especially it shows advantages when combined with PD-1/PD-L1 blockade. However, the mechanism by which anlotinib improves immunotherapy and remodeling of the tumor microenvironment remains unclear. In this study, we found that anlotinib combined with PD-1 blockade significantly inhibited tumor growth and reduced tumor weight in a lung cancer xenograft model compared to any single treatment. Both immunofluorescence and flow cytometry analyses revealed that anlotinib induced a CD8+ T cell dominated tumor microenvironment, which might account for its improved role in immunotherapy. Further investigations showed that CCL5-mediated CD8+ T cell recruitment plays a critical role in anlotinib and PD-1 blockade strategies. The depletion of CD8+ T cells abrogated this process. In conclusion, our findings showed that the combination of anlotinib and PD-1 blockade produced promising effects in the treatment of lung cancer, and that the induction of CCL5-mediced CD8+ T cell recruitment by anlotinib provided a novel mechanism of action.
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