Neutrophils in Cancer and Potential Therapeutic Strategies Using Neutrophil-Derived Exosomes

• Published in: Vaccines (Basel) Vol. 11; no. 6; p. 1028
• Main Authors: Dutta, Abhishek, Bhagat, Shrikrishna, Paul, Swastika, Katz, Jonathan P, Sengupta, Debomita, Bhargava, Dharmendra
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 26-05-2023; MDPI
• Subjects: Anticancer properties; Antitumor agents; Apoptosis; Arthritis; Asthma; Blood vessels; Bone marrow; Brain cancer; Cancer; Cancer therapies; Cancer vaccines; Chemokines; Complications and side effects; Crosstalk; Cytokines; Cytotoxicity; Exosomes; Extracellular matrix; Growth factors; Health aspects; Hydrogen peroxide; Immune response; immune suppression; Immune system; Immunosuppressive agents; Inflammation; Innate immunity; Leukocytes; Leukocytes (neutrophilic); Ligands; Medical prognosis; metastasis; miRNA; neutrophil-derived exosomes; Neutrophils; Pathogens; Patient outcomes; Peripheral circulation; Review; Therapeutic applications; Thromboembolism; Thrombosis; Tumor cells; tumor microenvironment; tumor-associated neutrophils; Tumors; India; trogocytosis; neutrophil-extracellular trap; metastasis; Neutrophils; tumor-associated neutrophils; neutrophil-derived exosomes; tumor microenvironment; immune suppression; ADCC and ADCP
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines11061028

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, H
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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.