Genome-derived cytosolic DNA mediates type I interferon-dependent rejection of B cell lymphoma cells

Cell Rep. 2015 Apr 21;11(3):460-73. doi: 10.1016/j.celrep.2015.03.041. Epub 2015 Apr 9.


The DNA damage response (DDR) induces the expression of type I interferons (IFNs), but the underlying mechanisms are poorly understood. Here, we show the presence of cytosolic DNA in different mouse and human tumor cells. Treatment of cells with genotoxic agents increased the levels of cytosolic DNA in a DDR-dependent manner. Cloning of cytosolic DNA molecules from mouse lymphoma cells suggests that cytosolic DNA is derived from unique genomic loci and has the potential to form non-B DNA structures, including R-loops. Overexpression of Rnaseh1, which resolves R-loops, reduced the levels of cytosolic DNA, type I Ifn transcripts, and type I IFN-dependent rejection of lymphoma cells. Live-cell imaging showed a dynamic contact of cytosolic DNA with mitochondria, an important organelle for innate immune recognition of cytosolic nucleotides. In summary, we found that cytosolic DNA is present in many tumor cells and contributes to the immunogenicity of tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Line
  • Cytosol / immunology
  • Cytosol / metabolism
  • DNA / immunology*
  • DNA Damage / immunology
  • HCT116 Cells
  • Humans
  • Interferon Type I / immunology*
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Real-Time Polymerase Chain Reaction


  • Interferon Type I
  • DNA