High Pretreatment Serum PD-L1 Levels Are Associated with Muscle Invasion and Shorter Survival in Upper Tract Urothelial Carcinoma

Programmed death ligand-1 (PD-L1) is an immune checkpoint molecule and a widely used therapeutic target in urothelial cancer. Its circulating, soluble levels (sPD-L1) were recently suggested to be associated with the presence and prognosis of various malignancies but have not yet been investigated i...

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Published in:Biomedicines 2022-10, Vol.10 (10), p.2560
Main Authors: Széles, Ádám, Kovács, Petra Terézia, Csizmarik, Anita, Váradi, Melinda, Riesz, Péter, Fazekas, Tamás, Váncsa, Szilárd, Hegyi, Péter, Oláh, Csilla, Tschirdewahn, Stephan, Darr, Christopher, Krafft, Ulrich, Grünwald, Viktor, Hadaschik, Boris, Horváth, Orsolya, Nyirády, Péter, Szarvas, Tibor
Format: Article
Language:English
Subjects:
biomarker
Biopsy
Bladder cancer
Cancer therapies
Chemotherapy
Decision making
Immune checkpoint inhibitors
Localization
Lymphatic system
Medical prognosis
Metastases
Metastasis
Patients
PD-L1 protein
Physiological aspects
prognosis
soluble programmed death ligand-1
sPD-L1
Survival
Therapeutic targets
Tumors
upper tract urothelial carcinoma
Urogenital system
Urothelial cancer
Urothelial carcinoma
UTUC
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Summary:Programmed death ligand-1 (PD-L1) is an immune checkpoint molecule and a widely used therapeutic target in urothelial cancer. Its circulating, soluble levels (sPD-L1) were recently suggested to be associated with the presence and prognosis of various malignancies but have not yet been investigated in upper tract urothelial carcinoma (UTUC). In this study, we assessed sPD-L1 levels in 97 prospectively collected serum samples from 61 UTUC patients who underwent radical nephroureterectomy (RNU), chemotherapy (CTX), or immune checkpoint inhibitor (ICI) therapy. In addition to pretreatment samples, postoperative and on-treatment sPD-L1 levels were determined in some patients by using ELISA. In the RNU group, elevated preoperative sPD-L1 was associated with a higher tumor grade (p = 0.019), stage (p < 0.001) and the presence of metastasis (p = 0.002). High sPD-L1 levels were significantly associated with worse survival in both the RNU and CTX cohorts. sPD-L1 levels were significantly elevated in postoperative samples (p = 0.011), while they remained unchanged during CTX. Interestingly, ICI treatment caused a strong, 25-fold increase in sPD-L1 (p < 0.001). Our results suggest that elevated preoperative sPD-L1 level is a predictor of higher pathological tumor stage and worse survival in UTUC, which therefore may help to optimize therapeutic decision-making. The observed characteristic sPD-L1 flare during immune checkpoint inhibitor therapy may have clinical significance.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines10102560