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Published on: January 22, 2013
PD-L1 as a Urine Biomarker in Renal Cell Carcinoma-A Case Series and Proof-of-Concept Study
Philipp Reimold1, Georgi Tosev1, Adam Kaczorowski2
1Department 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.
Insights
Urine PD-L1 levels are elevated in renal cell carcinoma (RCC) patients and correlate with treatment response. This study suggests urine PD-L1 may serve as a novel liquid biomarker for RCC detection and monitoring.
Area of Science:
- Uro-oncology
- Biomarker discovery
- Immunotherapy
Background:
- Metastatic renal cell carcinoma (mRCC) is a lethal malignancy.
- Immune checkpoint inhibitors (ICIs) targeting the PD-L1/PD-1 axis are current treatments for mRCC.
- High tumor PD-L1 expression is a negative prognostic factor, but its role as a liquid biomarker is underexplored.
Purpose of the Study:
- To investigate urine levels of PD-L1 in renal cell carcinoma (RCC) patients.
- To assess the correlation of urine PD-L1 with treatment response in metastatic RCC (mRCC).
- To evaluate urine PD-L1 as a potential liquid biomarker for treatment-naïve RCC.
Main Methods:
- Urine PD-L1 levels were measured using ELISA in treatment-naïve RCC patients (cohorts I and II) and mRCC patients.
- Urine PD-L1 was analyzed before and after ICI therapy or nephrectomy in mRCC patients.
- Exosomal PD-L1 was analyzed by immunoblotting in select patients.
Main Results:
- Urine PD-L1 levels significantly decreased after nephrectomy or ICI therapy in mRCC patients.
- Urine PD-L1 levels were significantly elevated in treatment-naïve RCC patients compared to controls (p=0.011).
- Elevated urine PD-L1 was particularly noted in low-grade RCCs; exosomal PD-L1 was detected in some patients.
Conclusions:
- PD-L1 is detectable in the urine of RCC patients.
- Urine PD-L1 levels correlate with treatment response in mRCC.
- Elevated urine PD-L1 may indicate the presence of treatment-naïve RCC.
