癌症中的中性粒细胞胞外诱捕网

癌症中的中性粒细胞胞外诱捕网

Neutrophil extracellular traps in cancer

作者:Muhammad H Shahzad, Roni F Rayes, Jonathan Cools-Lartigue, Jonathan D Spicer

期刊:Nature reviews. Cancer

摘要

在肿瘤免疫微环境（TIME）中，中性粒细胞可以通过NETosis过程释放中性粒细胞胞外诱捕网（NETs），这是一种蛋白质装饰的DNA网状结构，促进癌症的进展、转移和免疫逃逸。NETs通过在区域淋巴结中形成免疫抑制性、转移前的微环境，从而促进癌症的进展。在明显转移发生之前，NETs有助于在局部淋巴结中构建免疫抑制的预转移微环境。免疫检查点抑制剂、化疗和放疗等抗癌治疗可以诱导NETs的形成，这些NETs通过多种机制削弱抗肿瘤免疫反应并隔离肿瘤细胞，从而促进后续的癌症侵袭、迁移、转移及复发。针对NET负荷的精准血液和肿瘤检测可以为患者的预后和是否适合靶向NETosis、NETs和/或中性粒细胞的治疗提供信息。结合其他患者和治疗因素进行分期的重要性，将指导临床试验设计，以评估针对NET的治疗。在本综述中，我们强调了近年来对癌症中NET生物学的最新认识，突出转化研究数据的现有进展，以及对进一步临床试验以评估NET和NET靶向治疗的需求。

Abstract

Within the tumour immune microenvironment (TIME), neutrophils can undergo NETosis to release neutrophil extracellular traps (NETs), which are protein-decorated DNA webs that promote cancer progression, metastasis and immune evasion. NETs promote cancer progression by fostering an immunosuppressive, pre-metastatic niche in regional lymph nodes prior to overt metastasis. Anticancer therapies such as immune checkpoint inhibitors, chemotherapy and radiation therapy can induce the formation of NETs, which can facilitate subsequent cancer invasion, migration, metastasis and recurrence through several mechanisms that dampen antitumour immune responses and sequester neoplastic cells. Precision blood and tumour testing for the NET burden could inform both patient prognosis as well as eligibility for treatments aimed at targeting NETosis, NETs and/or neutrophils. The importance of staging with other patient and treatment factors will thus inform the design of clinical trials evaluating NET-directed therapies. In this Review, we highlight our recent understandings of NET biology in cancer, and emphasize the translational data available, as well as the need for further clinical trials evaluating NETs and NET-directed therapies.

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