Neutrophils in Cancer and Potential Therapeutic Strategies using Neutrophil-derived Exosomes

Abstract

Neutrophils are the most abundant immune cells and make up about 70% of white blood cells in human blood and play a critical role as the first line of defense in the innate immune response. They also help regulate the inflammatory environment to promote tissue repair. However, in cancer, neutrophils can be manipulated by tumors to either promote or hinder tumor growth depending on the cytokine pool. Studies have shown that tumor-bearing mice have increased levels of neutrophils in peripheral circulation, and that neutrophil-derived exosomes can deliver various cargos, including lncRNA and miRNA, which contribute to tumor growth and degradation of extracellular matrix. Exosomes derived from immune cells generally possess anti-tumor activities and induce tumor-cell apoptosis by delivering cytotoxic proteins, ROS generation, H2O2 or activation of Fas-mediated apoptosis in target cells. Engineered exosome-like nanovesicles have been developed to deliver chemotherapeutic drugs precisely to tumor cells. However, tumor-derived exosomes can aggravate cancer-associated thrombosis through the formation of neutrophil extracellular traps. Despite the advancements in neutrophil-related research, a detailed understanding of tumor-neutrophil crosstalk is still lacking and remains a major barrier in developing neutrophil-based or targeted therapy. This review will focus on the communication pathways between tumors and neutrophils, and the role of neutrophil-derived exosomes (NDEs) in tumor growth. Additionally, potential strategies to manipulate NDEs for therapeutic purposes will be discussed.

Constructing immune and prognostic features associated with ADCP in hepatocellular carcinoma and pan-cancer based on scRNA-seq and bulk RNA-seq

“…These differential genes were associated with granulocyte chemotaxis and migration, humoral immune responses mediated by circulating immunoglobulins, chemokines, and participated in the IL-17 signaling pathway. Neutrophils, crucial innate immune cells, play a key role in various diseases, including cancer ( 15 ). Bispecific antibody therapy could recruit cell types, including macrophages and neutrophils, as effector cells in cancer immunotherapy to induce ADCP ( 16 ).…”

“…In oncology research, rituximab has been shown to induce neutrophil-mediated phagocytosis of B-cell lymphoma cells. Indeed, neutrophil-mediated ADCP has been reported in various monoclonal antibody therapies, including obinutuzumab, ofatumumab, and trastuzumab ( 15 ). Macrophages, a crucial component of the innate immune system, are broadly categorized into two subtypes in the tumor microenvironment: the tumor-suppressing M1 type and the tumor-promoting M2 type.…”