2. Academic Validation
  3. B7-H3 augments the pro-angiogenic function of tumor-associated macrophages and acts as a novel adjuvant target for triple-negative breast cancer therapy

B7-H3 augments the pro-angiogenic function of tumor-associated macrophages and acts as a novel adjuvant target for triple-negative breast cancer therapy

  • Biochem Pharmacol. 2021 Jan;183:114298. doi: 10.1016/j.bcp.2020.114298.
Nan Cheng 1,  Yuncheng Bei 2,  Yue Song 1,  Weijie Zhang 3,  Lizhi Xu 1,  Wenlong Zhang 1,  Nanfei Yang 1,  Xuexia Bai 1,  Yuxin Shu 1,  Pingping Shen 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, School of Life Sciences, Nanjing University, Nanjing 210046, PR China.
  • 2 State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, PR China.
  • 3 Department of General Surgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210008, China.
  • 4 State Key Laboratory of Pharmaceutical Biotechnology and The Comprehensive Cancer Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, School of Life Sciences, Nanjing University, Nanjing 210046, PR China; Guangdong Key Laboratory of Genome Instability and Human Disease, Shenzhen University, Carson Cancer Center, Department of Biochemistry and Molecular Biology, Shenzhen University, School of Medicine, Shenzhen 518060, PR China. Electronic address: ppshen@nju.edu.cn.
PMID: 33153969 DOI: 10.1016/j.bcp.2020.114298
Abstract

B7-H3 is an immune checkpoint molecule from the B7 superfamily. It has been widely studied in tumor immune evasion in certain types of Cancer. In our preliminary study, we found that B7-H3 is specifically enriched in tumor-associated macrophages (TAMs) in triple-negative breast Cancer (TNBC) patients and strongly correlated with poor clinical prognosis. However, the role of B7-H3 in breast Cancer remains elusive. Our current study aims to explore the potential of B7-H3 as a novel target in TNBC therapy. Here, we demonstrated that B7-H3 enriched on TAMs is tightly correlated with TNBC clinical progression. B7-H3high TAMs exhibit great pro-metastatic and immunosuppressive functions by intriguing extracellular matrix (ECM) reconstruction and tumor angiogenesis, therefore helping tumor cell dissemination and dampening T-cell infiltration in tumor microenvironment (TME). Importantly, targeting blockade of B7-H3 by anti-B7-H3 antibody improves the tumor vasculature disorder, thereby enhancing chemotherapy and PD-1 therapy efficacy. In conclusion, our study establishes the correlation between B7-H3high TAMs and TNBC progression for the first time. By exploring the possibility of targeting B7-H3 expressed in both tumor cells and TAMs, we suggest that B7-H3 could be a promising target in clinical TNBC treatment.

Keywords

Angiogenesis; B7-H3; Combination cancer therapy; TAMs; TNBC.

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