Recurrent Loss of STING Signaling in Melanoma Correlates with Susceptibility to Viral Oncolysis - PubMed (original) (raw)
. 2016 Nov 15;76(22):6747-6759.
doi: 10.1158/0008-5472.CAN-16-1404. Epub 2016 Sep 28.
Affiliations
- PMID: 27680683
- DOI: 10.1158/0008-5472.CAN-16-1404
Recurrent Loss of STING Signaling in Melanoma Correlates with Susceptibility to Viral Oncolysis
Tianli Xia et al. Cancer Res. 2016.
Abstract
The innate immunoregulator STING stimulates cytokine production in response to the presence of cytosolic DNA, which can arise following DNA damage. Extrinsic STING signaling is also needed for antigen-presenting cells to stimulate antitumor T-cell immunity. Here, we show that STING signaling is recurrently suppressed in melanoma cells, where this event may enable immune escape after DNA damage. Mechanistically, STING signaling was suppressed most frequently by epigenetic silencing of either STING or the cyclic GMP-AMP synthase, which generates STING-activating cyclic dinucleotides after binding cytosolic DNA species. Loss of STING function rendered melanoma cells unable to produce type I IFN and other immune cytokines after exposure to cytosolic DNA species. Consequently, such cells were highly susceptible to infection with DNA viruses including HSV1, a variant of which is being developed presently as a therapeutic oncolytic virus [talimogene laherparepvec (T-VEC)]. Our findings provide insight into the basis for susceptibility to viral oncolysis by agents such as HSV1. Cancer Res; 76(22); 6747-59. ©2016 AACR.
©2016 American Association for Cancer Research.
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