中性粒细胞胞外诱捕网与口腔鳞状细胞癌关系的 研究进展  

Research progress on the association between neutrophil extracellular traps and oral squamous cell carcinoma

作　　者：杨圣锋 顾欣 张瑞[2] 宋红权[3] YANG Shengfeng;GU Xin;ZHANG Rui;SONG Hongquan(School of Stomatology,Harbin Medical University,Harbin 150001,China;Department of Stomatology,Nangang Branch of Heilongjiang Province Hospital,Harbin 150001,China;Oral Maxillofacial Department,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学口腔医学院,黑龙江哈尔滨150001 [2]黑龙江省医院南岗院区口腔科,黑龙江哈尔滨150001 [3]哈尔滨医科大学附属第一医院口腔颌面外科,黑龙江哈尔滨150001

出　　处：《口腔疾病防治》2024年第11期894-900,共7页Journal of Prevention and Treatment for Stomatological Diseases

基　　金：黑龙江省自然科学基金项目(LH2022H056);黑龙江省博士后科研启动金(LBH⁃Q21143);黑龙江省教育厅教育改革项目(SJGY20200455);黑龙江省卫生健康委科研课题(20210808020215)。

摘　　要：中性粒细胞胞外诱捕网(neutrophil extracellular traps,NETs)是中性粒细胞释放的一种由解聚的染色质和颗粒蛋白组成的纤维网状结构,可以捕获和杀死细菌。NETs的形成由各种细菌、病毒等病原体激活,其过程被称为网捕死亡(NETosis)。NETosis是一种不同于细胞凋亡和细胞坏死的细胞程序性死亡过程,目前已经报道了两种NETosis形式:裂解性NETosis和非裂解性NETosis。研究发现NETs能够在肿瘤微环境(tumor microenvironment,TME)中与免疫细胞相互作用,激活巨噬细胞;促进髓系抑制细胞的免疫抑制作用;并能包裹在肿瘤表面,防止CD8+T细胞和自然杀伤细胞发挥细胞毒性作用。近年研究发现,NETs在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)组织中大量存在,与OSCC发生发展关系复杂,根据不同的中性粒细胞表型,NETs可发挥促肿瘤或抗肿瘤作用,对N1型中性粒细胞,NETs可能是其发挥抗肿瘤作用的手段,而转换生长因子⁃β(transforming growth factor⁃β,TGF⁃β)诱导的NETs的形成可能与N2型中性粒细胞呈现促癌活性从而诱导口腔扁平苔藓恶变的机制有关。NETs还可能参与OSCC的转移过程,其通过捕获循环肿瘤细胞(circu⁃lating tumor cells,CTC)并诱导高凝状态促进肿瘤相关血栓的形成和血源性转移。NETs参与了OSCC发生和转移的过程,为抗肿瘤治疗和预测OSCC的预后提供了新的研究方向。抑制NETs的形成可以显著抑制化疗后产生的耐药性,并有利于降低OSCC患者的血栓形成风险从而抑制肿瘤转移。目前基于NETs相关基因已构建了多个关于头颈部鳞状细胞癌的预后模型。但目前NETs与OSCC的治疗尚处于讨论阶段,其作用机制与实行的可能性尚需大规模的基础与临床试验验证。本文通过综述NETs与OSCC之间的关系,为治疗OSCC提供新思路。Neutrophil extracellular traps(NETs)are fibrous web⁃like structures composed of decondensed chromatin and granular proteins released by neutrophils,with the ability to capture and kill bacteria.Pathogens,such as bacteria and viruses,can trigger the formation of NETs via NETosis,a type of programmed cell death that has two distinct forms:suicidal NETosis and vital NETosis.Numerous studies have found that NETs interact with immune cells in the tumor microenvironment,where they activate macrophages,promote immunosuppressive effects of myeloid⁃derived suppressor cells,and coat the tumor surface to prevent cytotoxic effects of CD8+T cells and natural killer cells.Recent research has identified a substantial presence of NETs in oral squamous cell carcinoma(OSCC)tissues,indicating a complex re⁃lationship between NETs and OSCC development.Depending on the phenotype of neutrophils,NETs may exhibit pro⁃tu⁃mor or anti⁃tumor effects.For instance,NETs derived from N1⁃type neutrophils may exert anti⁃tumor effects,while TGF⁃β⁃induced NETs derived from N2⁃type neutrophils may exert pro⁃carcinogenic activity,thereby contributing to the devel⁃opment of oral squamous metaplasia.Furthermore,NETs likely play a role in OSCC metastasis by capturing circulating tumor cells and inducing a hypercoagulable state,thereby facilitating tumor⁃related thrombus formation and hematoge⁃nous metastasis.The involvement of NETs in the occurrence and progression of OSCC opens new avenues for anti⁃tumor therapy and prognostication.Inhibiting NET formation can significantly suppress the development of chemotherapy⁃in⁃duced drug resistance and reduce the risk of thrombosis in OSCC patients,thereby inhibiting tumor metastasis.Current⁃ly,multiple prognostic models based on NET⁃related genes have been constructed and validated for head and neck squa⁃mous cell carcinoma,indicating the potential clinical value of NETs.However,the association between NETs and OSCC treatment is still unclear,necessitating further resea

关 键 词：中性粒细胞 中性粒细胞胞外诱捕网 巨噬细胞 CD8+T细胞 自然杀伤细胞 髓系抑制细胞 口腔鳞状细胞癌 肿瘤转移 肿瘤微环境 循环肿瘤细胞 化疗抵抗 髓过氧化物酶 游离DNA 

分 类 号：R78[医药卫生—口腔医学]