Urine PD-L1 as a non-invasive biomarker for immune checkpoint inhibitor (ICI) therapy in bladder cancer

Bladder cancer (BCa) is a common urological malignancy with a high recurrence rate, often within 2 years of initial diagnosis and treatment. Due to this high recurrence, near all patients require cystoscopic surveillance, which is invasive, uncomfortable, and costly. The cost of surveillance makes this cancer the most expensive cancer per case among all cancer types in the US. Therefore, early detection of recurrence or assessment of patients' response to treatment, particularly through non-invasive methods, is urgently needed. Since immune checkpoint inhibitors (ICIs) are widely used in many clinical trials for BCa treatment, having non-invasive and reliable biomarkers to select appropriate patients for ICI therapies or predict their treatment responses would be invaluable. Here we summarized the potential applications of programmed death-ligand 1 (PD-L1) from urine or urine BCa cell samples in BCa clinical settings. We discuss the use of both the free form of PD-L1 in urine samples and the expression levels of PD-L1 on the BCa cells shed in urine samples. Free PD-L1 can be measured with flow cytometry or ELISA-based approaches, while detecting PD-L1 on BCa cell surface requires isolating the urine-derived cancer cells and analyzing them via flow cytometry. Furthermore, we discuss the promising future research areas of urinary PD-L1 (uPD-L1) in bladder cancer, with a particular focus on the combination of conditional reprogramming cells (CRCs) technology and uPD-L1 studies, followed by an overview of several ongoing research topics. Based on current findings, uPD-L1 shows great potential as a versatile biomarker; however, further research is urgently needed to facilitate its translation into clinical applications.