How neutrophils shape the immune response of triple-negative breast cancer: Novel therapeutic strategies targeting neutrophil extracellular traps

Abstract

Triple-negative breast cancer (TNBC) is labeled as an aggressive type of breast cancer and still has limited therapeutic targets despite the advanced development of cancer therapy. Neutrophils, representing the conventional inflammatory response, significantly influence the malignant phenotype of tumors, supported by abundant evidence. As a vital function of neutrophils, NETs are the extracellular fibrous networks including the depolymerized chromatin DNA frames with several antimicrobial proteins. They are produced by activated neutrophils and are involved in host defence or immunological reactions. This review focuses more on the interactions between neutrophils and TNBC, focusing on how neutrophils modulate the immune response within the tumor milieu. Specifically, we delve into the role of NETs, which are involved in promoting tumor growth and metastasis, inhibiting anti-tumor immunity, and promoting tumor-associated thrombosis. Furthermore, we discuss recent advancements in therapeutic strategies aimed at targeting NETs to enhance the efficacy of TNBC treatment. The advances in the knowledge of the dynamics between neutrophils and TNBC may lead to the opportunity to devise new immunotherapeutic strategies targeted to fight this hostile type of breast cancer.

Keywords

• Neutrophil
• Neutrophil extracellular traps
• Triple-negative breast cancer
• Immune regulation
• Targeted therapy