Targeted activation of RNA helicase retinoic acid-inducible gene-I induces proimmunogenic apoptosis of human ovarian cancer cells
- PMID: 20551064
- DOI: 10.1158/0008-5472.CAN-10-0825
Targeted activation of RNA helicase retinoic acid-inducible gene-I induces proimmunogenic apoptosis of human ovarian cancer cells
Abstract
Most malignant cells are poorly immunogenic and fail to elicit an effective antitumor immune response. In contrast, viral infections of cells are promptly detected and eliminated by the immune system. Viral recognition critically hinges on cytosolic nucleic acid receptors that include the proinflammatory RNA helicase retinoic acid-inducible gene-I (RIG-I). Here, we show that targeted delivery of RIG-I agonists induced ovarian cancer cells to upregulate HLA class I and to secrete the proinflammatory cytokines CXCL10, CCL5, interleukin-6, tumor necrosis factor-alpha, and IFN-beta. Ovarian cancer cells stimulated via RIG-I became apoptotic and were readily phagocytosed by monocytes and monocyte-derived dendritic cells, which in turn upregulated HLA class I/II and costimulatory molecules and released CXCL10 and IFN-alpha. Our findings offer proof of principle that mimicking viral infection in ovarian cancer cells triggers an immunogenic form of tumor cell apoptosis that may enhance immunotherapy of ovarian cancer.
Copyright 2010 AACR.
Similar articles
-
Immunogenic cell death of human ovarian cancer cells induced by cytosolic poly(I:C) leads to myeloid cell maturation and activates NK cells.Eur J Immunol. 2011 Oct;41(10):3028-39. doi: 10.1002/eji.201141555. Epub 2011 Aug 30. Eur J Immunol. 2011. PMID: 21728171
-
Targeting the cytosolic innate immune receptors RIG-I and MDA5 effectively counteracts cancer cell heterogeneity in glioblastoma.Stem Cells. 2013 Jun;31(6):1064-74. doi: 10.1002/stem.1350. Stem Cells. 2013. PMID: 23390110
-
Retinoic acid-inducible gene-I is induced by double-stranded RNA and regulates the expression of CC chemokine ligand (CCL) 5 in human mesangial cells.Nephrol Dial Transplant. 2010 Nov;25(11):3534-9. doi: 10.1093/ndt/gfq270. Epub 2010 May 19. Nephrol Dial Transplant. 2010. PMID: 20484300
-
Approaching the RNA ligand for RIG-I?Immunol Rev. 2009 Jan;227(1):66-74. doi: 10.1111/j.1600-065X.2008.00724.x. Immunol Rev. 2009. PMID: 19120476 Review.
-
[Cell type specific involvement of RIG-I in antiviral responses].Nihon Rinsho. 2006 Jul;64(7):1244-7. Nihon Rinsho. 2006. PMID: 16838639 Review. Japanese.
Cited by
-
High RIG-I expression in ovarian cancer associates with an immune-escape signature and poor clinical outcome.Int J Cancer. 2020 Apr 1;146(7):2007-2018. doi: 10.1002/ijc.32818. Epub 2019 Dec 19. Int J Cancer. 2020. PMID: 31800094 Free PMC article.
-
Toll-like receptor, RIG-I-like receptors and the NLRP3 inflammasome: key modulators of innate immune responses to double-stranded RNA viruses.Cytokine Growth Factor Rev. 2011 Apr;22(2):63-72. doi: 10.1016/j.cytogfr.2011.02.001. Epub 2011 Apr 3. Cytokine Growth Factor Rev. 2011. PMID: 21466970 Free PMC article. Review.
-
Harnessing RIG-I and intrinsic immunity in the tumor microenvironment for therapeutic cancer treatment.Oncotarget. 2018 Jun 22;9(48):29007-29017. doi: 10.18632/oncotarget.25626. eCollection 2018 Jun 22. Oncotarget. 2018. PMID: 29989043 Free PMC article. Review.
-
Duplex RNA activated ATPases (DRAs): platforms for RNA sensing, signaling and processing.RNA Biol. 2013 Jan;10(1):111-20. doi: 10.4161/rna.22706. Epub 2012 Dec 10. RNA Biol. 2013. PMID: 23228901 Free PMC article. Review.
-
DNA Repair Deficiency in Breast Cancer: Opportunities for Immunotherapy.J Oncol. 2019 Jun 19;2019:4325105. doi: 10.1155/2019/4325105. eCollection 2019. J Oncol. 2019. PMID: 31320901 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
