The Feasibility and Diagnostic Adequacy of PD-L1 Expression Analysis Using the Cytoinclusion Technique in Bladder Cancer: A Prospective Single-Center Study Luca Di Gianfrancesco, Isabella Monia Montagner, Debora Tormen, Alessandro Crestani, Antonio Amodeo, et al. Journal of Clinical Medicine, 2024 Background: Programmed death-ligand 1 (PD-L1) expression has been recognized as a potential biomarker for various cancers, yet its diagnostic and prognostic significance in urothelial bladder cancer (BCa) requires further investigation. Methods: In this prospective single-center study, we aimed to assess the feasibility and diagnostic adequacy of PD-L1 expression analysis using cytoinclusion in BCa patients. We enrolled consecutive patients undergoing endoscopic transurethral resection of bladder tumor (TURBT), repeat TURBT, or robot-assisted radical cystectomy. Urinary and tissue specimens were collected from these patients for cytoinclusion and histopathological analysis to evaluate PD-L1 expression. Results: Out of 29 patients, PD-L1 expression was detected from cytoinclusion in 42.8% (3 out of 7), 10% (1 out of 10), and 66.8% (8 out of 12) of patients with negative/papilloma, low-grade, and high-grade tumors, respectively. Conversely, histopathological analysis identified PD-L1 expression in 57.2% (4 out of 7), 30% (3 out of 10), and 83.3% (10 out of 12) of patients with negative/papilloma, low-grade, and high-grade tumors, respectively. The diagnostic concordance between cytoinclusion and histopathology was 85.7%, 80%, and 83.3% in patients with negative/papilloma, low-grade, and high-grade tumors, respectively. Conclusions: Our study underscores the promise of cytoinclusion as a minimally invasive method for quantifying urinary PD-L1 percentages. This approach could serve as both a potential prognostic and diagnostic indicator, easily obtainable from urine samples. Standardizing this technique could facilitate its widespread use as a valuable tool.
The Role of Checkpoint Inhibitor Expression Directly on Exfoliated Cells from Bladder Cancer: A Narrative Review Luca Di Gianfrancesco, Alessandro Crestani, Antonio Amodeo, Paolo Corsi, Davide De Marchi, et al. Diagnostics, 2023 Bladder cancer (BCa) is a common type of cancer that affects the urinary bladder. The early detection and management of BCa is critical for successful treatment and patient outcomes. In recent years, researchers have been exploring the use of biomarkers as a non-invasive and effective tool for the detection and monitoring of BCa. One such biomarker is programmed death-ligand 1 (PD-L1), which is expressed on the surface of cancer cells and plays a crucial role in the evasion of the immune system. Studies have shown that the PD-L1 expression is higher in BCa tumors than in healthy bladder tissue. Additionally, PD-L1 expression might even be detected in urine samples in BCa patients, in addition to the examination of a histological sample. The technique is being standardized and optimized. We reported how BCa patients had higher urinary PD-L1 levels than controls by considering BCa tumors expressing PD-L1 in the tissue specimen. The expression of PD-L1 in urinary BCa cells might represent both a diagnostic and a prognostic tool, with the perspective that the PD-L1 expression of exfoliate urinary cells might reveal and anticipate eventual BCa recurrence or progression. Further prospective and longitudinal studies are needed to assess the expression of PD-L1 as a biomarker for the monitoring of BCa patients. The use of PD-L1 as a biomarker for the detection and monitoring of BCa has the potential to significantly improve patient outcomes by allowing for earlier detection and more effective management of the disease.
Composite tumour of the stomach: a case report and review of the literature Chirurgia Italiana, 2005
Lymphocytes endowed with colon-selective homing and engineered to produce TGF-β1 prevent the development of dinitrobenzene sulphonic acid colitis Ignazio Castagliuolo, Paola Brun, Deborah Tormen, Giorgio Pal?? European Journal of Gastroenterology and Hepatology, 2003 Background Gene therapy is an attractive approach to the treatment of inflammatory diseases. However, the lack of tissue targeting of available vectors jeopardizes their clinical use. Aims Since α4β7 integrin mediates lymphocyte homing to the intestinal mucosa, we tested the possibility of in-vitro engineering α4β7-bearing lymphocytes to restrict the production of a therapeutic cytokine, transforming growth factor (TGF)-β1, to within the colonic mucosa. Methods Lymphocytes were isolated from colonic lamina propria or spleen and transfected with either pC1 or pC1/TGF-β1. Results Transfected spleen and lamina propria cells released TGF-β1 for up to 5 days in vitro and administration of 107 spleen cells, but not 106 lamina propria or spleen cells, to normal mice caused a significant rise in circulating TGF-β1. Following intrarectal injection of dinitrobenzene sulphonic acid, intraperitoneal administration of lamina propria or spleen cells transfected with pC1/TGF-β1, but not pC1, significantly reduced colitis-associated body weight loss, colonic myeloperoxidase (MPO) activity, interleukin-1β levels, and macroscopic and microscopic inflammatory damage. Vector-specific TGF-β1 mRNA transcripts were detectable in the colon and liver following injection of lamina propria lymphocytes, and in the spleen, liver and colon following administration of spleen lymphocytes. Incubation of pC1/TGF-β1-transfected lamina propria lymphocytes with anti-α4β7 integrin antibody blocked their protective effects and caused the disappearance of vector-specific TGF-β1 transcripts from the colonic mucosa. Conclusion We conclude that lymphocytes are an efficient vehicle for transient gene therapy and that cells bearing α4β7 integrins preferentially deliver therapeutic genes to the colonic mucosa.
