Fig. 1.

An overview of the various triggers for tumor cell-intrinsic inflammatory signaling and the downstream response. Various cell-intrinsic triggers can result in the release of endogenous DNA, RNA, or DNA-RNA hybrids in the cytosol, including chromosomal instability, DNA damage, mitochondrial dysfunction, defects in nucleic acid clearance/processing, and R-loops. These “out-of-place” nucleic acids activate DNA and/or RNA sensors, resulting in inflammatory signaling. Consequently, the expression of type I IFNs and NF-κB target genes are induced. ADAR1, adenosine deaminase acting on RNA 1; cGAS, cyclic GMP-AMP synthase; 2′3′-cGAMP, cyclic GMP-AMP; DNA-PK, DNA-dependent protein kinase; IFI16, interferon-γ inducible 16; IFN, interferon; IKK, IκB kinase; IRF3/7, interferon regulatory factor 3/7; MAVS, mitochondrial antiviral signaling protein; MDA5, melanoma differentiation-associated protein 5; MRE11, meiotic recombination 11; NF-κB, nuclear factor κ-light-chain-enhancer of activated B cells; RIG-I, retinoic acid-inducible gene-I; STING, stimulator of interferon genes; TBK1, TANK-binding kinase 1; TREX1, three prime repair exonuclease 1