PD-L1 as a Urine Biomarker in Renal Cell Carcinoma-A Case Series and Proof-of-Concept Study

PD-L1 作为肾细胞癌尿液生物标志物 - 病例系列和概念验证研究

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作者: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

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

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.

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

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.

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