Abstract B19: Targeting ATM to sensitize pancreatic cancer to immunotherapy and radiotherapy

Abstract

Combinatorial strategies are needed to overcome the resistance of pancreatic cancer to immune checkpoint blockade (ICB). DNA damage activates the innate immune response and improves ICB efficacy. We have studied the role of ATM, a core component of the DNA damage response, on pancreatic tumor immunogenicity in vitro and in vivo. Inhibition of ATM increased tumoral interferon signaling in a cGAS/STING-independent but TBK1 and SRC-dependent manner. The combination of ATM inhibition with radiation enhanced TBK1 activity, T1IFN production, and antigen presentation in vitro. Furthermore, ATM silencing enhanced T-cell trafficking in vivo and increased the sensitivity of pancreatic tumors to PD-L1 blocking antibody. The potential of ATM as a target for combinatorial strategy with ICB and radiation in pancreatic cancer will be discussed. Citation Format: Michael Green, Qiang Zhang, Xueting Lang, Yu Lei, Theodore S. Lawrence, Weiping Zou, Meredith A. Morgan. Targeting ATM to sensitize pancreatic cancer to immunotherapy and radiotherapy [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B19.