DNA damage responses in time and space: Implications for cancer immunotherapy

DNA damage induces multiple cellular signals, including marked chromatin remodelling that collectively activate DNA repair mechanisms and cell cycle checkpoints. Our work explores how this acute DNA damage response contributes to transcriptional changes and reorganization of nuclear structure. DNA damage responses also lead to transcriptional rewiring of cells to initiate prolonged production of inflammatory cytokines. We have identified a mechanism by which these inflammatory signals are activated. We further show the importance of these inflammatory signalling pathways in treatments that combine radiotherapy with immune checkpoint blockade. In this seminar we will explore connections between these acute and delayed DNA damage responses and the implications for cancer treatments.