Himcinschi Mihai Emanuel, Uscatescu Valentina, Gherghe Georgiana, Stoian Irina, Vlad Adelina, Popa Delia Codruța, Coriu Daniel, Anghel Andrei
Department of Biochemistry and Pharmacology, Discipline of Biochemistry, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania.
Department of Hematology, Fundeni Clinical Institute, 022328 Bucharest, Romania.
Diagnostics (Basel). 2024 Feb 2;14(3):328. 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.
中性粒细胞胞外陷阱（NETs）最初被发现是宿主对细菌固有免疫反应的一部分。它们形成一种网状结构，可固定微生物或展现出直接的抗菌特性，比如释放活性氧（ROS）。当中性粒细胞在暴露于ROS、趋化因子、细胞因子或其他可溶性因子后经历某种细胞死亡时，NETs便会形成。这个过程导致中性粒细胞的DNA以网状形式释放，上面装饰有瓜氨酸化组蛋白（H3/H4-cit）、中性粒细胞弹性蛋白酶（NE）和髓过氧化物酶（MPO）。新兴研究表明，NETs在肿瘤学中发挥着重要作用，因为它们被证明会影响肿瘤生长、恶性起始和增殖，介导从内皮组织到间充质组织的转变，刺激血管生成或转移，甚至能帮助癌细胞逃避免疫反应。NETs在癌症治疗中的作用在于它们能够形成并充当一种机械屏障，使原发性肿瘤对辐射或药物渗透的反应降低。随后，研究表明，在进行药物治疗时，癌细胞会内化NETs并将其用作强大的抗氧化剂。在这篇综述中，我们探讨了NETs作为肿瘤微环境（TME）一部分在恶性上皮瘤背景下的作用，恶性上皮瘤能够自主产生CA215（一种IgG亚变体，属于癌胚抗原（CEA）超家族的一部分）。研究表明，CA215具有一个功能性Fc亚区，能够激活中性粒细胞表面的Fc-γ-RS受体。这种激活随后可能刺激NETs的产生，从而表明CA215是癌症治疗监测中的一个潜在因素。
