Recurrent loss of STING signaling in melanoma correlates with susceptibility to viral oncolysis

Tianli Xia, Hiroyasu Konno, Glen N Barber

Research output: Contribution to journalArticle

68 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6747-6759
Number of pages13
JournalCancer Research
Volume76
Issue number22
DOIs
StatePublished - Nov 15 2016

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Melanoma
GMP synthase (glutamine-hydrolyzing)
DNA Damage
DNA Virus Infections
DNA
Oncolytic Viruses
Cytokines
Antigen-Presenting Cells
Epigenomics
Immunity
T-Lymphocytes
Therapeutics
cyclic guanosine monophosphate-adenosine monophosphate

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Recurrent loss of STING signaling in melanoma correlates with susceptibility to viral oncolysis. / Xia, Tianli; Konno, Hiroyasu; Barber, Glen N.

In: Cancer Research, Vol. 76, No. 22, 15.11.2016, p. 6747-6759.

Research output: Contribution to journalArticle

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