Journal Article

Schlafen 5 is an intracellular immune checkpoint and controls interferon responses in pancreatic ductal adenocarcinoma

Hryhorysak, Briana N, Blyth, Gavin T, Baran, Aneta H, Lee-Chang, Catalina, Miska, Jason M, Patel, Priyam, Saleiro, Diana, Zannikou, Markella, Castro, Brandyn A, Kocherginsky, Masha, Eckerdt, Frank, Beauchamp, Elspeth M, Fischietti, Mariafausta, Platanias, Leonidas C, Guillen Magaña, Jamie N, Bartom, Elizabeth T, Lopez Fajardo, Emely

2026

Overview

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 macrophages (TAMs) alongside an increase in tumor infiltrating effector cells in tumors over time. These findings implicate SLFN5 acts as an intracellular immune checkpoint and identify it as a unique therapeutic target for the development of therapies for PDAC and possibly other malignancies.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 macrophages (TAMs) alongside an increase in tumor infiltrating effector cells in tumors over time. These findings implicate SLFN5 acts as an intracellular immune checkpoint and identify it as a unique therapeutic target for the development of therapies for PDAC and possibly other malignancies.