The Role of Neutrophil Extracellular Traps in the Outcome of Malignant Epitheliomas: Significance of CA215 Involvement

• Published in: Diagnostics (Basel) 2024-02, Vol.14 (3), p.328
• Main Authors: Himcinschi, Mihai Emanuel, Uscatescu, Valentina, Gherghe, Georgiana, Stoian, Irina, Vlad, Adelina, Popa, Delia Codruța, Coriu, Daniel, Anghel, Andrei
• Format: Article
• Language: English
• Subjects: Blood vessels; CA215; Cancer; cancer therapy resistance; CEA (Oncology); Cytokines; Development and progression; DNA binding proteins; Enzymes; epithelioma; Extracellular matrix; Health aspects; Histones; IgG; Immune response; Immune system; Immunoglobulin G; Immunotherapy; Inflammation; Leukocytes; Metastasis; NETosis; neutrophil extracellular traps (NETs); Neutrophils; Pathogens; Proteins; Vascular endothelial growth factor
• ISSN: 2075-4418; 2075-4418
• DOI: 10.3390/diagnostics14030328

Neutrophil extracellular traps (NETs) were originally discovered as a part of the innate immune response of the host to bacteria. They form a web-like structure that can immobilize microorganisms or exhibit direct antimicrobial properties, such as releasing reactive oxygen species (ROS). NETs are established when neutrophils undergo a sort of cellular death following exposure to ROS, chemokines, cytokines, or other soluble factors. This process results in the release of the neutrophil's DNA in a web-like form, which is decorated with citrullinated histones (H3/H4-cit), neutrophil elastase (NE), and myeloperoxidase (MPO). Emerging studies have put into perspective that NETs play an important role in oncology as they were shown to influence tumor growth, malignant initiation, and proliferation, mediate the transition from endothelial to mesenchymal tissue, stimulate angiogenesis or metastasis, and can even help cancer cells evade the immune response. The role of NETs in cancer therapy resides in their ability to form and act as a mechanical barrier that will provide the primary tumor with a reduced response to irradiation or pharmaceutical penetration. Subsequently, cancer cells are shown to internalize NETs and use them as a strong antioxidant when pharmaceutical treatment is administered. In this review, we explored the role of NETs as part of the tumor microenvironment (TME), in the context of malignant epitheliomas, which are capable of an autonomous production of CA215, a subvariant of IgG, and part of the carcinoembryonic antigen (CEA) superfamily. Studies have shown that CA215 has a functional Fc subdivision able to activate the Fc-gamma-RS receptor on the surface of neutrophils. This activation may afterward stimulate the production of NETs, thus indicating CA215 as a potential factor in cancer therapy surveillance.