Urine-derived lymphocytes as a non-invasive measure of the bladder tumor immune microenvironment

Area of Science:

• Oncology
• Immunology
• Urothelial Carcinomas

Background:

• Cancer immunotherapy, particularly checkpoint blockade, shows limited efficacy in a subset of bladder cancer patients.
• Understanding the tumor immune microenvironment (TME) is crucial for improving treatment outcomes, but direct tumor access is often limited.
• Identifying accessible biomarkers is essential for predicting response and guiding treatment strategies in muscle-invasive bladder cancer (MIBC).

Purpose of the Study:

• To investigate urine-derived lymphocytes (UDLs) as a non-invasive surrogate for the bladder tumor immune microenvironment (TME) in patients with MIBC.
• To assess the correlation between UDL composition and the TME's immune checkpoint landscape and T cell receptor (TCR) repertoire.
• To evaluate the prognostic value of UDLs in predicting recurrence-free survival after cystectomy.

Main Methods:

• Analysis of UDLs isolated from urine samples of 32 patients with MIBC.
• Flow cytometry to characterize T cell subsets (CD8+, CD4+, regulatory T cells) and immune checkpoint expression (e.g., PD-1).
• T cell receptor (TCR) sequencing to assess the repertoire diversity and clonality within UDLs and correlate with TME.

Main Results:

• UDLs were identified as a readily accessible source of T cells in MIBC patients.
• The immune checkpoint profile and TCR repertoire of UDLs accurately reflected those found within the tumor microenvironment.
• An increased UDL count, particularly CD8+ T cells with high PD-1 expression (PD-1hi), at cystectomy correlated with shorter recurrence-free survival.

Conclusions:

• UDL analysis serves as a dynamic liquid biopsy, providing a representative snapshot of the bladder immune TME.
• UDL profiling can identify actionable immuno-oncology (IO) targets.
• UDL analysis holds potential prognostic value for predicting outcomes in MIBC patients.