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

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

in Animals / Carcinoma, Pancreatic Ductal - genetics / Carcinoma, Pancreatic Ductal - immunology / Carcinoma, Pancreatic Ductal - metabolism / Carcinoma, Pancreatic Ductal - pathology / Cell Line, Tumor / Female / Humans / Interferon Type I - immunology / Interferon Type I - metabolism / Mice / Pancreatic Neoplasms - genetics / Pancreatic Neoplasms - immunology / Pancreatic Neoplasms - metabolism / Pancreatic Neoplasms - pathology / Tumor-Associated Macrophages - immunology

2026

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

2026

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

2026

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Journal Article

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

Hryhorysak, Briana N.,

Miska, Jason M.,

Lee-Chang, Catalina,

Platanias, Leonidas C.,

Baran, Aneta H.,

Patel, Priyam,

Saleiro, Diana,

Zannikou, Markella,

Bartom, Elizabeth T.,

Kocherginsky, Masha,

Magaña, Jamie N. Guillen,

Fajardo, Emely Lopez,

Eckerdt, Frank,

Fischietti, Mariafausta,

Castro, Brandyn A.,

Beauchamp, Elspeth M.,

Blyth, Gavin T.

2026

Overview

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.

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Publisher

American Society for Clinical Investigation

Subject

Animals

/ Carcinoma, Pancreatic Ductal - genetics

/ Carcinoma, Pancreatic Ductal - immunology

/ Carcinoma, Pancreatic Ductal - metabolism

/ Carcinoma, Pancreatic Ductal - pathology

/ Cell Line, Tumor

/ Female