# BCG immunotherapy for bladder cancer triggers systemic and local BCG-specific CD4+ Th1 responses

## TL;DR

This study shows that BCG treatment for bladder cancer boosts CD4+ Th1 immune cells both in the blood and bladder, offering new insights into how this therapy works.

## Contribution

The study reveals that BCG-specific CD4+ Th1 cells are present before treatment and increase during therapy, with evidence of their recruitment to the bladder.

## Key findings

- Pre-existing BCG-specific CD4+ T cells are detectable in treatment-naive patients.
- BCG therapy increases the frequency and memory differentiation of BCG-specific CD4+ T cells.
- BCG-specific CD4+ Th1 cells are detectable in urine during treatment, indicating bladder recruitment.

## Abstract

High-risk non-muscle-invasive bladder cancer (NMIBC) is treated with intravesical instillations of Bacillus Calmette-Guérin (BCG), which trigger a local immune response. Improved patient outcomes have been linked to the recruitment of CD4+ T helper type 1 (Th1) cells to the bladder. However, specific antigens recognized by the bladder-infiltrating T cells remain largely unknown. In this study, we followed thirty-two patients with NMIBC undergoing BCG immunotherapy. Longitudinal blood and urine samples were collected to investigate the dynamics and characteristics of BCG-specific T cells. We detected pre-existing BCG-specific CD4+ T cells in most BCG therapy-naive patients before treatment induction. BCG immunotherapy increased the frequency and memory differentiation of circulating BCG-specific CD4+ T cells, which displayed a polyfunctional Th1 phenotype. Importantly, we provide evidence that BCG-specific CD4+ Th1 cells can be detected in urine during therapy, suggesting their recruitment to the bladder. This study provides novel biological insights into the cellular mechanisms of BCG-induced immunity in bladder cancer.

•Pre-existing BCG-specific CD4+ T cells are detectable in treatment-naive patients•BCG therapy increases frequency and differentiation of BCG-specific CD4+ T cells•BCG-specific CD4+ T cells show a polyfunctional Th1 cytokine profile•BCG-specific CD4+ Th1 cells are detectable in urine during treatment

Pre-existing BCG-specific CD4+ T cells are detectable in treatment-naive patients

BCG therapy increases frequency and differentiation of BCG-specific CD4+ T cells

BCG-specific CD4+ T cells show a polyfunctional Th1 cytokine profile

BCG-specific CD4+ Th1 cells are detectable in urine during treatment

Immunology; oncology; therapeutics; immune response