High Serum PD-L1 Levels Are Associated with Poor Survival in Urothelial Cancer Patients Treated with Chemotherapy and Immune Checkpoint Inhibitor Therapy

血清 PD-L1 水平高与接受化疗和免疫检查点抑制剂治疗的尿路上皮癌患者生存率低有关

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作者:Ulrich Krafft, Csilla Olah, Henning Reis, Claudia Kesch, Christopher Darr, Viktor Grünwald, Stephan Tschirdewahn, Boris Hadaschik, Orsolya Horvath, Istvan Kenessey, Peter Nyirady, Melinda Varadi, Orsolya Modos, Anita Csizmarik, Tibor Szarvas

Abstract

Serum PD-L1 (sPD-L1) levels are associated with prognosis in various tumors but has not yet been investigated in advanced bladder cancer. We assessed pretreatment serum samples from 83 BC patients who received platinum chemotherapy and from 12 patients who underwent immune checkpoint inhibitor (ICI) therapy. In addition, on-treatment samples from further therapy cycles were collected during chemotherapy (n = 58) and ICI therapy (n = 11). Serum PD-L1 levels were determined using ELISA. High baseline sPD-L1 levels were associated with worse ECOG status (p = 0.007) and shorter overall survival for both chemotherapy- and ICI-treated patients (p = 0.002 and p = 0.040, respectively). Multivariate analysis revealed high baseline sPD-L1 level as an independent predictor of poor survival for platinum-treated patients (p = 0.002). A correlation analysis between serum concentrations of PD-L1 and matrix metalloprotease-7 (MMP-7)-a protease which was recently found to cleave PD-L1-revealed a positive correlation (p = 0.001). No significant sPD-L1 changes were detected during chemotherapy, while in contrast we found a strong, 25-fold increase in sPD-L1 levels during atezolizumab treatment. In conclusion, our work demonstrates that pretreatment sPD-L1 levels are associated with a poor prognosis of BC patients undergoing platinum and ICI therapy. Future research should prospectively address the value of sPD-L1 in predicting treatment response.

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