# Type I-interferon β induces a strong anti-tumour response in bladder cancer cells

## TL;DR

This study shows that interferon-β strongly activates immune responses in bladder cancer cells, potentially improving treatment outcomes.

## Contribution

The study identifies IFN-β as the most effective interferon type in activating immune pathways in bladder cancer cells.

## Key findings

- IFN-β activates the JAK/STAT pathway more effectively than other interferons in bladder cancer cells.
- Long-term treatment with type I and III IFNs increases ISG expression and induces apoptosis in BLCA cells.
- IFN-β's activation is mediated by ISRE, highlighting its role in immunomodulation.

## Abstract

For non-muscle invasive bladder cancer (NMIBC), instillation with Bacillus Calmette-Guérin (BCG) is a standard therapy. With a still unclear mechanism, instillation activates the innate immune system, resulting in an immunological effect on the tumour. The aim of this work was to investigate which bladder cancer (BLCA) cells can be activated by interferon (IFN) exposure.

The BLCA cell lines RT4 and SW780 were stimulated with IFN-α2, -β and -λ1 over 4–72 h. Quantitative PCR (qPCR) was used to determine the expression of IFN receptor subunits (RS) and selected interferon-stimulated genes (ISGs). Luciferase reporter assay was performed to detect the activation of the IFN responsive element (ISRE). Different signal transduction molecules of the JAK/STAT pathway were assessed by Western Blot to prove its activation in BLCA cells. The viability of the stimulated cells was measured by WST-1 assay and the apoptosis induction by caspase-3/7 assay.

The JAK/STAT pathway was activated via the four RS. Upon long-term treatment, type I and type III IFNs significantly induced increased ISG expression and apoptosis induction of RT4 and SW780 cells, emphasising their antiproliferative and immunomodulatory activity. This activation was mediated by ISRE. IFN-β activated the JAK/STAT pathway with the greatest potency, highlighting its superior efficacy in modulating cellular responses in BLCA.

Activation of the innate immune system has the ability to trigger further infiltration of the tumour microenvironment (TME) with immune cells, which positively influence the TME in its type, density and immunofunctional orientation against BLCA.

The online version contains supplementary material available at 10.1007/s00432-025-06409-1.