PD-L1 as a Urine Biomarker in Renal Cell Carcinoma—A Case Series and Proof-of-Concept Study
Philipp Reimold,
Georgi Tosev,
Adam Kaczorowski,
Jana Friedhoff,
Constantin Schwab,
Viktoria Schütz,
Magdalena Görtz,
Niklas Panzer,
Martina Heller,
Cem Aksoy,
Ruth Himmelsbach,
Thomas Walle,
Stefanie Zschäbitz,
Dirk Jäger,
Anette Duensing,
Albrecht Stenzinger,
Markus Hohenfellner,
Stefan Duensing
Affiliations
Philipp Reimold
Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 420, D-69120 Heidelberg, Germany
Georgi Tosev
Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 420, D-69120 Heidelberg, Germany
Adam Kaczorowski
Molecular Urooncology, University Hospital Heidelberg, Im Neuenheimer Feld 517, D-69120 Heidelberg, Germany
Jana Friedhoff
Molecular Urooncology, University Hospital Heidelberg, Im Neuenheimer Feld 517, D-69120 Heidelberg, Germany
Constantin Schwab
Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, D-69120 Heidelberg, Germany
Viktoria Schütz
Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 420, D-69120 Heidelberg, Germany
Magdalena Görtz
Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 420, D-69120 Heidelberg, Germany
Niklas Panzer
Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 420, D-69120 Heidelberg, Germany
Martina Heller
Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 420, D-69120 Heidelberg, Germany
Cem Aksoy
Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 420, D-69120 Heidelberg, Germany
Ruth Himmelsbach
Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 420, D-69120 Heidelberg, Germany
Thomas Walle
Department of Medical Oncology, University Hospital Heidelberg and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, D-69120 Heidelberg, Germany
Stefanie Zschäbitz
Department of Medical Oncology, University Hospital Heidelberg and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, D-69120 Heidelberg, Germany
Dirk Jäger
Department of Medical Oncology, University Hospital Heidelberg and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, D-69120 Heidelberg, Germany
Anette Duensing
Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 420, D-69120 Heidelberg, Germany
Albrecht Stenzinger
Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, D-69120 Heidelberg, Germany
Markus Hohenfellner
Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 420, D-69120 Heidelberg, Germany
Stefan Duensing
Department of Urology, University Hospital Heidelberg, Im Neuenheimer Feld 420, D-69120 Heidelberg, Germany
Background: Renal cell carcinoma (RCC) is among the most lethal urologic malignancies once metastatic. Current treatment approaches for metastatic RCC (mRCC) involve immune checkpoint inhibitors (ICIs) that target the PD-L1/PD-1 axis. High PD-L1 expression in tumor tissue has been identified as a negative prognostic factor in RCC. However, the role of PD-L1 as a liquid biomarker has not yet been fully explored. Herein, we analyze urine levels of PD-L1 in mRCC patients before and after either ICI therapy or surgical intervention, as well as in a series of patients with treatment-naïve RCC. Patients and Methods: The mid-stream urine of patients with mRCC (n = 4) or treatment-naïve RCC, i.e., prior to surgery from two centers (cohort I, n = 49: cohort II, n = 29) was analyzed for PD-L1 by ELISA. The results from cohort I were compared to a control group consisting of patients treated for non-malignant urologic diseases (n = 31). In the mRCC group, urine PD-L1 levels were measured before and after tumor nephrectomy (n = 1) or before and after ICI therapy (n = 3). Exosomal PD-L1 in the urine was analyzed in selected patients by immunoblotting. Results: A strong decrease in urine PD-L1 levels was found after tumor nephrectomy or following systemic treatment with ICIs. In patients with treatment-naïve RCC (cohort I), urine PD-L1 levels were significantly elevated in the RCC group in comparison to the control group (median 59 pg/mL vs. 25.7 pg/mL, p = 0.011). PD-L1 urine levels were found to be elevated, in particular, in low-grade RCCs in cohorts I and II. Exosomal PD-L1 was detected in the urine of a subset of patients. Conclusion: In this proof-of-concept study, we show that PD-L1 can be detected in the urine of RCC patients. Urine PD-L1 levels were found to correlate with the treatment response in mRCC patients and were significantly elevated in treatment-naïve RCC patients.
