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

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:

Published: January 2021

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-H3 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-H3 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.

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Source
http://dx.doi.org/10.1016/j.bcp.2020.114298DOI Listing

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