Ovarian cancer cells commonly exhibit defective STING signaling which affects sensitivity to viral oncolysis

Nina Marí Gual Pimenta De Queiroz, Tianli Xia, Hiroyasu Konno, Glen N Barber

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Ovarian cancer is the sixth most prevalent cancer in women and the most lethal of the gynecologic malignancies. Treatments have comprised the use of immunotherapeutic agents as well as oncolytic viruses, with varying results for reasons that remain to be clarified. To better understand the mechanisms that may help predict treatment outcome, we have evaluated innate immune signaling in select ovarian cancer cell lines, governed by the Stimulator of Interferon Genes (STING), which controls self or viral DNA-triggered cytokine production. Our results indicate that STING-dependent signaling is habitually defective in majority of ovarian cancer cells examined, frequently through the suppression of STING and/or the cyclic dinucleotide (CDN) enzyme Cyclic GMP-AMP synthase (cGAS) expression, by epigenetic processes. However, STINGindependent, dsRNA-activated innate immune cytokine production, which require RIG-I/MDA5, were largely unaffected. Such defects enabled ovarian cancer cells to avoid DNA damage-mediated cytokine production, which would alert the immunosurveillance system. Loss of STING signaling also rendered ovarian cancer cells highly susceptible to viral oncolytic g34.5 deleted-HSV1 (Herpes simplex virus) infection in vitro and in vivo. Implications: STING signaling evaluation in tumors may help predict disease outcome and possibly dictate the efficacy of oncoviral and other types of cancer therapies.

Original languageEnglish (US)
Pages (from-to)974-986
Number of pages13
JournalMolecular Cancer Research
Volume17
Issue number4
DOIs
StatePublished - Jan 1 2019

Fingerprint

Ovarian Neoplasms
Interferons
GMP synthase (glutamine-hydrolyzing)
Genes
Cytokines
Neoplasms
Genetic Epigenesis
Oncolytic Viruses
Immunologic Monitoring
Viral DNA
Virus Diseases
Simplexvirus
DNA Damage
Cell Line
Enzymes
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Ovarian cancer cells commonly exhibit defective STING signaling which affects sensitivity to viral oncolysis. / De Queiroz, Nina Marí Gual Pimenta; Xia, Tianli; Konno, Hiroyasu; Barber, Glen N.

In: Molecular Cancer Research, Vol. 17, No. 4, 01.01.2019, p. 974-986.

Research output: Contribution to journalArticle

De Queiroz, Nina Marí Gual Pimenta ; Xia, Tianli ; Konno, Hiroyasu ; Barber, Glen N. / Ovarian cancer cells commonly exhibit defective STING signaling which affects sensitivity to viral oncolysis. In: Molecular Cancer Research. 2019 ; Vol. 17, No. 4. pp. 974-986.
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