Immunogenic cell death of human ovarian cancer cells induced by cytosolic poly(I:C) leads to myeloid cell maturation and activates NK cells

Kirsten Kübler, Carola tho Pesch, Nadine Gehrke, Soheila Riemann, Juliane Daßler, Christoph Coch, Jennifer Landsberg, Vera Wimmenauer, Martin Pölcher, Christian Rudlowski, Thomas Tüting, Walther Kuhn, Gunther Hartmann, Winfried Barchet

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Owing to high rates of tumor relapse, ovarian cancer remains a fatal disease for which new therapeutic approaches are urgently needed. Accumulating evidence indicates that immune stimulation may delay or even prevent disease recurrence in ovarian cancer. In order to elicit proinflammatory signals that induce or amplify antitumor immune reactivity, we mimicked viral infection in ascites-derived ovarian cancer cells. By transfection or electroporation we targeted the synthetic double-stranded RNA poly(I:C) intracellularly in order to activate melanoma differentiation-associated gene-5 (MDA-5), a sensor of viral RNA in the cytosol of somatic cells. Cancer cells reacted with enhanced expression of HLA-class I, release of CXCL10, IL-6, and type I IFN as well as tumor cell apoptosis. Monocytes and monocyte-derived DCs (MoDCs) engulfed MDA-5-activated cancer cells, and subsequently upregulated HLA-class I/II and costimulatory molecules, and secreted CXCL10 and IFN-α. Further, this proinflammatory milieu promoted cytolytic activity and IFN-γ secretion of NK cells. Thus, our data suggest that the engagement of MDA-5 in a whole tumor cell vaccine is a promising approach for the immunotherapy of ovarian cancer.

Original languageEnglish
Pages (from-to)3028-3039
Number of pages12
JournalEuropean Journal of Immunology
Volume41
Issue number10
DOIs
StatePublished - Oct 2011
Externally publishedYes

Keywords

  • Innate immunity
  • MDA-5
  • Ovarian cancer
  • Poly(I:C)
  • Tumor immunogenicity

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