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Journal Article Research Support, Non-U.S. Gov't Epublish 23 citations

PubMed: 35990640 DOI: 10.3389/fimmu.2022.937924

Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy.

Front Immunol 13:937924

Authors: Peng Fan, Huiping Qiang, Zhenhua Liu, Qi Zhao, Ying Wang, Tingkun Liu, Xuan Wang, Tianqing Chu, Yuhui Huang, Wei Xu, Songbing Qin

Affiliations

  • Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China. Department of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy.
  • Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
  • Department of Radiotherapy, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.
  • Department of Immunology, Innovent Biologics, Inc. Suzhou, China.

Abstract

Anlotinib is a new multitarget tyrosine kinase inhibitor for tumor angiogenesis, and its monotherapy exhibits a decent clinical efficacy. However, the process of combining Anlotinib and immune checkpoint therapy to achieve optimal antitumor effects while limiting side effects remains unclear. In this study, we found that effective low-dose Anlotinib was sufficient to inhibit tumor growth while reducing side effects compared with high doses. Effective low-dose Anlotinib treatments induced durable tumor vascular normalization and improved anti-PD-1 therapy in both short- and long-term treatment regimens. Mechanistically, the combination therapy increased the proportions of intratumoral CD4 T, CD8 T, and NK cells. Anlotinib-associated antitumor effects were independent of interferon γ; however, the combination therapy required CD8 T cells to suppress tumor growth. Together, these results suggest that the combination of effective low-dose Anlotinib and PD-1 blockade induces durable antitumor effects with fewer side effects. Our findings indicate that antiangiogenic treatments combined with immune checkpoint therapy at an effective low-dose, rather than a tolerable high dose, would be more efficacious and safer.

MeSH

Growth, Immune System Diseases, Cells, Therapeutics, Neoplasms, Exhibitions As Topic

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