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

## TL;DR

This paper shows that Schlafen 5 (SLFN5) suppresses immune responses in pancreatic cancer and could be a new target for treatment.

## Contribution

The study identifies SLFN5 as an intracellular immune checkpoint in pancreatic cancer, offering a novel therapeutic target.

## Key findings

- Blocking Slfn5 in pancreatic cancer enhanced IFN responses and suppressed tumor growth in mice.
- SLFN5 promotes an immunosuppressive tumor microenvironment by modulating immune cell infiltration.

## Abstract

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.

Slfn5 is target and modulator of Type I IFN responses, and promotes an immunosuppressive tumor microenvironment.