Schlafen 5 (SLFN5) is an Intracellular Immune Checkpoint and controls Interferon (IFN) Responses in Pancreatic Ductal Adenocarcinoma (PDAC)

We provide evidence that human and murine SLFN5 proteins are modulators of Type I IFN responses and the immune response in pancreatic cancer. Blocking expression of Slfn5 in PDAC enhances IFN-responses, suppresses tumor growth, and prolongs survival in immunocompetent mice. Notably, immunophenotypic analysis reveals a reduction in tumor-associated myeloid cells (TAMCs) alongside an increase in tumor infiltrating effector cells in tumors. These findings implicate SLFN5 acts as an intracellular immune checkpoint and identify it as a unique therapeutic target for the development of novel therapies for PDAC and possibly other malignancies Overall design: RNA-Seq profiling of wildtype PANC-1 cells and SLFN5 knockout derivatives untreated or treated with interferon alpha (5,000 IU) for 6 hours