2. Academic Validation
  3. Anlotinib enhanced CD8+ T cell infiltration via induction of CCL5 improves the efficacy of PD-1/PD-L1 blockade therapy in lung cancer

Anlotinib enhanced CD8+ T cell infiltration via induction of CCL5 improves the efficacy of PD-1/PD-L1 blockade therapy in lung cancer

  • Cancer Lett. 2024 Apr 18:591:216892. doi: 10.1016/j.canlet.2024.216892.
Jie Luo 1,  Kebin Cheng 2,  Xianxiu Ji 3,  Caixia Gao 4,  Ren Zhu 5,  Jiayi Chen 6,  Wenjun Xue 7,  Qi Huang 8,  Qingqiang Xu 9
Affiliations

Affiliations

  • 1 Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China. Electronic address: lj_1342@163.com.
  • 2 Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
  • 3 Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
  • 4 Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
  • 5 Department of Medical Administration, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China.
  • 6 Department of Pharmacy, Traditional Chinese Medicine Hospital of Yangpu District, Shanghai, China.
  • 7 School of Medicine, Tongji University, Shanghai, 200070, China.
  • 8 Basic Medical Center for Pulmonary Disease, Faculty of Naval Medicine, Naval Medical University, Shanghai, 200433, China.
  • 9 Basic Medical Center for Pulmonary Disease, Faculty of Naval Medicine, Naval Medical University, Shanghai, 200433, China. Electronic address: qingqiangxu@smmu.edu.cn.
PMID: 38621459 DOI: 10.1016/j.canlet.2024.216892
Abstract

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.

Keywords

Anlotinib; CD8(+) T cells; Lung cancer; PD-1 antibody.

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