Diagnostics (Mar 2024)

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

DOI
https://doi.org/10.3390/diagnostics14070741
Journal volume & issue
Vol. 14, no. 7
p. 741

Abstract

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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.

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