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

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.

Soluble PD-L1 in Serum and Urine in Urinary Bladder Cancer Patients

“…Supporting data for increased levels of sPD-L1 in patients with metastatic disease has also been reported in other cancer types, such as non-small cell lung cancer and renal cell cancer [ 28 , 29 ]. High sPD-L1 levels were also associated with all-cause mortality in the present study, which is in line with data from Krafft et al, reporting sPD-L1 as an independent predictor of overall survival in patients with BC [ 21 ]. However, no association between sPD-L1 and cancer-specific death was found in the present study, possibly due to the small number of events, leaving the study without power for investigating this association.…”

“…These results suggest that serum sPD-L1 levels increase with a more aggressive disease. Krafft et al, reported significantly higher levels of serum sPD-L1 among patients with high stage BC (T3–T4) compared to patients with low stage disease (T0–T2), although they found no association between sPD-L1 and lymphatic or visceral metastases [ 21 ]. Supporting data for increased levels of sPD-L1 in patients with metastatic disease has also been reported in other cancer types, such as non-small cell lung cancer and renal cell cancer [ 28 , 29 ].…”

“…Soluble PD-L1 is thought to retain its ability to bind membrane bound PD-1, and thus could inhibit T cell activation and proliferation [ 17 ]. Soluble PD-L1 has previously been detected in blood from patients with various cancers [ 18 , 19 , 20 ], and recently it was reported that sPD-L1 could also be detected in serum and urine samples in BC [ 21 , 22 ]. Further studies are however needed in order to investigate sPD-L1 in BC patients and our aims were to investigate if sPD-L1 levels in serum and urine could be a potential diagnostic and/or prognostic biomarker in BC.…”

A novel signature constructed by ferroptosis-associated genes (FAGs) for the prediction of prognosis in bladder urothelial carcinoma (BLCA) and associated with immune infiltration

“…There was an increasing body of evidence suggested that immune regulation played an important role in bladder cancer, including PD-1, PD-L1, tumor-associated macrophages, myeloid-derived suppressor cells, regulatory T cells and so on [ 6 ]. Ulrich et al demonstrated that higher pretreatment serum PD-L1 (sPD-L1) levels were related to the poor prognosis in patients following platinum and immune checkpoint inhibitor treatments [ 54 ]. Jiang et al revealed that M2 and PD-1-positive Tumor-associated macrophages were connected with poor clinical results in muscle invasive bladder cancer patients, and the blinding of PD-1 and CD68 could stimulate tumor growth [ 55 ].…”

Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma

“…Soluble PD-1/PD-L1 was suggested as a diagnostic, therapeutic and prognostic biomarker in different cancers (summarized in [ 10 ]), indicating, e.g., an impaired outcome and treatment response in patients with multiple myeloma [ 11 ]. Moreover, in a series of papers, different authors recently suggested a role of sPD-L1 as a biomarker in very different cancer entities and have suggested a diagnostic, prognostic and predictive role of this molecular marker in cancers originating from the urothelium, lung and brain [ 12 , 13 , 14 ]. In addition, sPD-L1 was found to be a prognostic marker in gastrointestinal stromal cancers and gastric cancers [ 15 , 16 ].…”