PMID- 27680683
OWN - NLM
STAT- MEDLINE
DCOM- 20170911
LR  - 20180728
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 76
IP  - 22
DP  - 2016 Nov 15
TI  - Recurrent Loss of STING Signaling in Melanoma Correlates with Susceptibility to
      Viral Oncolysis.
PG  - 6747-6759
LID - 10.1158/0008-5472.CAN-16-1404 [doi]
AB  - 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. (c)2016 AACR.
CI  - (c)2016 American Association for Cancer Research.
FAU - Xia, Tianli
AU  - Xia T
AD  - Department of Cell Biology and the Sylvester Comprehensive Cancer Center,
      University of Miami Miller School of Medicine, Miami, Florida.
FAU - Konno, Hiroyasu
AU  - Konno H
AD  - Department of Cell Biology and the Sylvester Comprehensive Cancer Center,
      University of Miami Miller School of Medicine, Miami, Florida.
FAU - Barber, Glen N
AU  - Barber GN
AD  - Department of Cell Biology and the Sylvester Comprehensive Cancer Center,
      University of Miami Miller School of Medicine, Miami, Florida.
      gbarber@med.miami.edu.
LA  - eng
PT  - Journal Article
DEP - 20160928
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
SB  - IM
MH  - Animals
MH  - Humans
MH  - Melanoma/*immunology
MH  - Mice
MH  - Oncolytic Viruses/*immunology
MH  - Signal Transduction
EDAT- 2016/11/05 06:00
MHDA- 2017/09/12 06:00
CRDT- 2016/09/30 06:00
PHST- 2016/05/19 00:00 [received]
PHST- 2016/08/29 00:00 [revised]
PHST- 2016/09/08 00:00 [accepted]
PHST- 2016/11/05 06:00 [pubmed]
PHST- 2017/09/12 06:00 [medline]
PHST- 2016/09/30 06:00 [entrez]
AID - 0008-5472.CAN-16-1404 [pii]
AID - 10.1158/0008-5472.CAN-16-1404 [doi]
PST - ppublish
SO  - Cancer Res. 2016 Nov 15;76(22):6747-6759. doi: 10.1158/0008-5472.CAN-16-1404.
      Epub 2016 Sep 28.