1. Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University,Shanghai,China,200032
2. Department of Immunology, School of Basic Medical Sciences, Fudan University,Shanghai,China,200032
3. Laboratory of Tumor Immunology, Department of Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Fudan University,Shanghai,China,200032
4. Center for Novel Target and Therapeutic Intervention, Chongqing Medical University,Chongqing,China,400016
5. Department of Pathology, Zhongshan Hospital, Fudan University,Shanghai,China,200032
6. Department of Urology, Zhongshan Hospital, Fudan University,Shanghai,China,200032
7. Department of Urology, Zhongshan Hospital Wusong Branch, Fudan University,Shanghai,China,200940
Published:2023,
Published Online:1 November 2023,
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Jiaqi Wang, Jiying Zhu, Junchi Hu, et al. A novel in vitro prognostic model of bladder cancer based on urine-derived living tumor cells. [J]. Genes & Diseases 1(6):2586-2596(2023)
Jiaqi Wang, Jiying Zhu, Junchi Hu, et al. A novel in vitro prognostic model of bladder cancer based on urine-derived living tumor cells. [J]. Genes & Diseases 1(6):2586-2596(2023) DOI: 10.1016/j.gendis.2022.10.022.
Bladder cancer (BLCA) remains a difficult malignancy to manage because of its high recurrence
intense follow-up
and invasive diagnostic and treatment techniques. Immune checkpoint inhibitors (ICIs) have forged a new direction for the treatment of BLCA
but it is currently challenging to predict whether an individual patient will be sensitive to ICIs. We collected 43 urine/tumor samples from BLCA patients for primary bladder cancer cells (BCCs) culturing using our previously reported BCC culture platform. We used flow cytometry (FCM) to measure the expression levels of Programmed Death-Ligand 1 (PD-L1) on BCCs before and after interferon-gamma (IFN-γ) treatment and found that PD-L1 expression and the sensitivities to IFN-γ varied among patients. RNA-sequencing
western blotting
and programmed death-1 (PD-1) binding assays confirmed that the BCC FCM-based PD-L1 detection platform (BC-PD-L1) was reliable and was not hindered by the glycosylation of PD-L1. In the subsequent retrospective study
we found that IFN-γ-stimulated PD-L1 (sPD-L1) expression on BCCs detected by BC-PD-L1 could predict the prognosis of BLCA patients. Importantly
the prognostic value was similar or even better in urine-derived BC-PD-L1 (UBC-PD-L1). Transcriptome analysis showed that BCCs with high sPD-L1 tended to enrich genes associated with the collagen-containing extracellular matrix
cell–cell adhesion
and positive regulation of the immune system. In addition
the UBC-PD-L1 also exhibited predictive value for ICI response in BLCA patients. In conclusion
as a novel personalized urine-detection method
UBC-PD-L1 may provide a rapid
accurate
and non-invasive tool for monitoring tumor progression
predicting therapeutic responses
and helping improve BLCA clinical treatment in future.
Bladder cancerImmune checkpoint inhibitorsPredictive modelPrimary cellsUrine
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