Elena A Samishina1, Ekaterina V Blinova2, Dmitry A Roshchin3, Irina R Suslova4, Dmitry S Blinov1, Pavel N Zhdanov1, Olga N Deryabina5, Olesia V Kit’ko4
1Department of General Pathology, Laboratory of Pharmacology, All-Union Scientific Center for Biological Active Compounds Safety, Staraja Kupavna, Russia
2Department of Clinical Anatomy, Sechenov University, Moscow; Department of Pharmacology, Laboratory of Molecular Pharmacology, National Research Ogarev Mordovia State University, Saransk, Russia
3Department of Oncological Urology, Russian National Research Medical Centre of Radiology, Moscow, Russia
4Department of Clinical Anatomy, Sechenov University, Moscow, Russia
5Department of Pharmacology, Laboratory of Molecular Pharmacology, National Research Ogarev Mordovia State University, Saransk, Russia
DOI: 10.4103/jcar.JCar_3_19
ABSTRACT
CONTEXT: Exploration of the biological property of programmed death-ligand 1 (PD-L1) signaling that may impact bladder tumor growth in humanized animals and cell culture.
AIMS: The aim of this study is to evaluate how PD-L1 signaling involves bladder cancer growth and progression.
SETTINGS AND DESIGN: This study design involves experimental in vivo and in vivo study.
SUBJECTS AND METHODS: A role of PD-L1 signaling pathway inhibition for bladder cancer growth was assessed in humanized immunodeficient animals carried main molecular subtypes of bladder carcinoma patient-derived xenografts and provided with selective anti-PD-L1 treatment; bladder cancer cells invasiveness was evaluated in mixed RT112/84 cells + CD4+ cells culture incubated with PD-L1 blocker durvalumab. We used two-tailed Student’s t-test to explore differences between main and control subgroups. Significance of intergroup comparison was measured with one-way ANOVA followed by the Tukey’s or Newman–Keul’s criterion. Survival curves were analyzed with Gehan’s criterion with the Yate’s correction. Differences were considered statistically significant at P < 0.05.
RESULTS: Anti-PD-L1 intervention increased survival of the animals carried both primary and relapsed luminal noninvasive, muscular invasive, and relapsed luminal bladder cancer xenografts. There was significant retardation of tumor volume duplication time in aforementioned subgroups correlated with PD-L1 expression. Durvalumab treatment in concentration-dependent manner inhibited tumor cells invasiveness of mixed RT112 + CD4+ culture cells with its maximum at the highest studied concentration (10 μM).
CONCLUSIONS: Obtained data constituted the pivotal role of programmed cell death-1/PD-L1 signaling pathway in bladder cancer development and progression. The results will have major implications for further clinical investigations.
Keywords: Anti-programmed death-ligand 1 treatment, invasiveness, metastasis, nonmuscular invasive bladder cancer, patient-derived xenograft