Radiation-dependent Nucleic Acid Sensing, and Its Possible Impact on Radiotherapy

DNA damage and chromosomal instability can promote sterile inflammatory responses in cells, similar to those induced by pathogen infection. Primary contributors to this phenomenon are cGAS-dependent and AIM2-dependent DNA-sensing mechanisms, as well as RIG-I-dependent, MDA5-dependent, and ZBP1-dependent RNA-sensing mechanisms. Work over the last decade has established that some or all of these pathways may also be activated by radiotherapy, potentially modulating the behavior of irradiated tumours. With an emphasis on tumor cells, we review here how innate immune signalling may become activated during radiotherapy, and how it may impact the behavior of irradiated cells, as well as how this might pattern the tumor microenvironment.