Cytosolic DNA Sensing in Organismal Tumor Control

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 cellu...

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Published inCancer cell Vol. 34; no. 3; pp. 361 - 378
Main Authors Vanpouille-Box, Claire, Demaria, Sandra, Formenti, Silvia C., Galluzzi, Lorenzo
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 10.09.2018
Subjects
apoptosis
CGAS
inflammasome
micronuclei
mtDNA
necroptosis
pyroptosis
STING
type I interferon
ZBP1
type I interferon
ZBP1
pyroptosis
mtDNA
inflammasome
apoptosis
CGAS
STING
micronuclei
necroptosis
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Summary: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. 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.
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ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccell.2018.05.013