Antiangiogenic therapy reverses the immunosuppressive breast cancer microenvironment

Wuzhen Chen; Lesang Shen; Jingxin Jiang; Leyi Zhang; Zhigang Zhang; Jun Pan; Chao Ni; Zhigang Chen

doi:10.1186/s40364-021-00312-w

Antiangiogenic therapy reverses the immunosuppressive breast cancer microenvironment

Biomark Res. 2021 Jul 22;9(1):59. doi: 10.1186/s40364-021-00312-w.

Authors

Wuzhen Chen^{1

2}, Lesang Shen^{1

2}, Jingxin Jiang^{1

2}, Leyi Zhang², Zhigang Zhang², Jun Pan², Chao Ni^{3

4}, Zhigang Chen^{5

6}

Affiliations

¹ Department of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310000, Zhejiang Province, China.
² Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China.
³ Department of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310000, Zhejiang Province, China. nicaho428@zju.edu.cn.
⁴ Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China. nicaho428@zju.edu.cn.
⁵ Department of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310000, Zhejiang Province, China. chenzhigang@zju.edu.cn.
⁶ Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China. chenzhigang@zju.edu.cn.

Abstract

Tumor angiogenesis induces local hypoxia and recruits immunosuppressive cells, whereas hypoxia subsequently promotes tumor angiogenesis. Immunotherapy efficacy depends on the accumulation and activity of tumor-infiltrating immune cells (TIICs). Antangiogenic therapy could improve local perfusion, relieve tumor microenvironment (TME) hypoxia, and reverse the immunosuppressive state. Combining antiangiogenic therapy with immunotherapy might represent a promising option for the treatment of breast cancer. This article discusses the immunosuppressive characteristics of the breast cancer TME and outlines the interaction between the tumor vasculature and the immune system. Combining antiangiogenic therapy with immunotherapy could interrupt abnormal tumor vasculature-immunosuppression crosstalk, increase effector immune cell infiltration, improve immunotherapy effectiveness, and reduce the risk of immune-related adverse events. In addition, we summarize the preclinical research and ongoing clinical research related to the combination of antiangiogenic therapy with immunotherapy, discuss the underlying mechanisms, and provide a view for future developments. The combination of antiangiogenic therapy and immunotherapy could be a potential therapeutic strategy for treatment of breast cancer to promote tumor vasculature normalization and increase the efficiency of immunotherapy.

Keywords: Antiangiogenic therapy; Breast cancer; Immunotherapy; Tumor microenvironment (TME).

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Review

Abstract

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