Schlafen 5 is an intracellular immune checkpoint and controls IFN responses in pancreatic ductal adenocarcinoma
We provide evidence that human and murine Schlafen 5 (SLFN5) proteins are modulators of type I IFN responses and the immune response in pancreatic ductal adenocarcinoma (PDAC). Blocking expression of Slfn5 in PDAC enhanced IFN responses, suppressed tumor growth, and prolonged survival in immunocompetent mice. Notably, immunophenotypic analysis revealed a reduction in tumor-associated macrophages alongside an increase in tumor-infiltrating effector cells in tumors over time. These findings suggest 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.
Authors
- Markella Zannikou
- Mariafausta Fischietti
- Brandyn A. Castro
- Leonidas C. Platanias
- Masha Kocherginsky
- Frank Eckerdt
- Priyam Patel
- Gavin T. Blyth
- Jamie N. Guillen Magaña
- Diana Saleiro
- Jason M. Miska
- Aneta H. Baran
- Elspeth M. Beauchamp
- Elizabeth T. Bartom
- Catalina Lee-Chang
- Emely Lopez Fajardo
- Briana N. Hryhorysak
Institutions
- Northwestern University (US)
- Laboratory of Molecular Genetics (PL)
- Jesse Brown VA Medical Center (US)
Publication Details
- Journal
- JCI Insight
- Published
- 2026-01-27
- DOI
- https://doi.org/10.1172/jci.insight.190031
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Northwestern University
- National Institutes of Health
- National Cancer Institute