Session

Overview: This symposium is positioned to highlight connections between the DNA damage response and immune responses. DNA damage caused by radiation is known to result in micronuclei due in part to acentrometric DNA fragments that escape normal mitotic segregation. Such micronuclei can recruit pattern recognition receptors such as cGAS, and thereby launch innate immunity signaling pathways that have the potential to boost response to immune therapy. However, much remains unknown about DNA damage sensing and signal transduction, as well as the promise of therapeutic approaches that leverage these responses. In this session, Dr. Shane Harding will provide insights into how DNA damage can affect micronuclei composition and cytokine signaling in response to irradiation. This will be followed by two talks converging on the consequences of ATR/ATM inhibition on immunomodulation. Dr. Randi Syljuåsen will focus on the aspect of apoptotic caspases and their roles in response to low- and high-LET irradiation. Dr. Kevin Harrington will show the latest results of the combination of ATR inhibition with radiotherapy and immunotherapy in animal models and clinical trials. Finally, Dr. Claus Sørensen will delineate how DNA damage checkpoint pathways suppress innate immunity signaling, with consequences for leveraging emerging druggable targets. As such, this session will provide novel insights into DNA damage recognition and signal transduction to immune modulatory pathways, with perspectives on combination treatments that seek to leverage these responses and vulnerabilities.