机体肿瘤控制中的细胞质 DNA 感应。

Cytosolic DNA Sensing in Organismal Tumor Control.

机构信息

Department of Radiation Oncology, Weill Cornell Medical College, Stich Radiation Oncology, 525 East 68th Street, Box #169, New York, NY 10065, USA.

Department of Radiation Oncology, Weill Cornell Medical College, Stich Radiation Oncology, 525 East 68th Street, Box #169, New York, NY 10065, USA; Sandra and Edward Meyer Cancer Center, New York, NY, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.

出版信息

Cancer Cell. 2018 Sep 10;34(3):361-378. doi: 10.1016/j.ccell.2018.05.013. Epub 2018 Jun 28.

DOI:10.1016/j.ccell.2018.05.013

PMID:30216189

Abstract

Besides constituting a first layer of defense against microbial challenges, the detection of cytosolic DNA is fundamental for mammalian organisms to control malignant transformation and tumor progression. The accumulation of DNA in the cytoplasm can initiate the proliferative inactivation (via cellular senescence) or elimination (via regulated cell death) of neoplastic cell precursors. Moreover, cytosolic DNA sensing is intimately connected to the secretion of cytokines that support innate and adaptive antitumor immunity. Here, we discuss the molecular mechanisms whereby cytosolic DNA enables cell-intrinsic and -extrinsic oncosuppression, and their relevance for the development of novel therapeutic approaches that reinstate anticancer immunosurveillance.

摘要

除了构成抵御微生物挑战的第一道防线外，细胞质 DNA 的检测对于哺乳动物机体控制恶性转化和肿瘤进展也是至关重要的。细胞质中 DNA 的积累可以启动肿瘤前体细胞的增殖失活（通过细胞衰老）或消除（通过细胞凋亡）。此外，细胞质 DNA 的感应与支持先天和适应性抗肿瘤免疫的细胞因子的分泌密切相关。在这里，我们讨论了细胞质 DNA 使细胞内和细胞外抗肿瘤抑制的分子机制，以及它们对恢复抗肿瘤免疫监视的新型治疗方法的发展的相关性。