Abstract
Introduction and hypothesis
The objective was to assess PD-L1 expression in nonbacterial chronic cystitis (NCC) and bladder cancer (BC).
Methods
The present study included 20 NCC and 20 BC patients. The degree of inflammation of the bladder wall was assessed on slides stained with H&E. Viral pathogens (herpes simplex virus, Epstein–Barr virus, cytomegalovirus, and high-risk HPVs) were detected using real-time polymerase chain reaction analyses of the bladder specimens. Immunohistochemistry was performed to assess the PD-L1 expression in bladder tissue.
Results
Expression of PD-L1 was detected in 40% of NCC patients and 85% of BC patients. Viral pathogens were found in 50% of NCC patients and 60% of BC patients, with EBV being the most common. In NCC patients the immune cell score correlated strongly with the degree of inflammatory infiltration of the bladder wall (r = 0.867, p < 0.001), the presence of lymphoid aggregates in the submucosa (r = 0.804, p < 0.001), koilocytosis (r = 0.620, p = 0.004), and the presence of viral pathogens (r = 0.784, p < 0.001). In BC patients the immune cell score correlated with the degree of inflammatory infiltration of the bladder wall (r = 0.534, p = 0.015) and the presence of viral pathogens (r = 0.626, p = 0.003), but not with the presence of lymphoid aggregates in the submucosa (r = 0.083, p = 0.729), and koilocytosis (r = 0.366, p = 0.112).
Conclusions
Expression of PD-L1 was detected in a cohort of NCC patients, although the PD-L1 positivity rate was lower than that in BC. Our results demonstrate that the degree of PD-L1 expression in bladder tissue is associated with the presence of viral infections and with the degree of inflammatory infiltration of the bladder wall in both NCC and BC.
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Data availability
The authors confirm that all data generated or analyzed during this study are available within the article.
Abbreviations
- BC:
-
Bladder cancer
- CMV:
-
Cytomegalovirus
- EBV:
-
Epstein–Barr virus
- HPV:
-
Human papillomavirus
- HSV:
-
Herpes simplex virus
- IC/BPS:
-
Interstitial cystitis/bladder pain syndrome
- IUC:
-
Infiltrating urothelial carcinoma
- NCC:
-
Nonbacterial chronic cystitis
- NPUC:
-
Non-invasive papillary urothelial carcinoma
- PCR:
-
Polymerase chain reaction
- PD-1:
-
Programmed death-1
- PD-L1:
-
Programmed death ligand-1
- TC score:
-
Tumor cell score
References
Barsegian VA, Kosova IV. Role of the lower urinary tract viral infections in the development of female micturition disorders. Urologiia. 2022;5:117–22.
Odabasi Z, Mert A. Candida urinary tract infections in adults. World J Urol. 2020;38(11):2699–707. https://doi.org/10.1007/s00345-019-02991-5.
Jhang JF, Hsu YH, Peng CW, Jiang YH, Ho HC, Kuo HC. Epstein-Barr virus as a potential etiology of persistent bladder inflammation in human interstitial cystitis/bladder pain syndrome. J Urol. 2018;200(3):590–6. https://doi.org/10.1016/j.juro.2018.03.133.
Hsu CY, Lin CL, Kao CH. Association between chronic interstitial cystitis and herpes zoster. Int J Environ Res Public Health. 2020;17(7):2228. https://doi.org/10.3390/ijerph17072228.
Chen Y, Yu W, Yang Y, et al. Expression of programmed death ligand-1 on bladder tissues is detected in a clinically and histologically well-defined interstitial cystitis cohort. Neurourol Urodyn. 2018;37(4):1396–404. https://doi.org/10.1002/nau.23459.
Schönrich G, Raftery MJ. The PD-1/PD-L1 axis and virus infections: a delicate balance. Front Cell Infect Microbiol. 2019;13(9):207. https://doi.org/10.3389/fcimb.2019.00207.
Patsoukis N, Wang Q, Strauss L, Boussiotis VA. Revisiting the PD-1 pathway. Sci Adv. 2020;6(38):eabd2712. https://doi.org/10.1126/sciadv.abd2712.
Han Y, Liu D, Li L. PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res. 2020;10(3):727–42.
Szczepaniak K, Paskal W, Kuśmierczyk Z, et al. Evaluation of spatial PD1 and PD-L1 expression in inflammatory bowel disease samples—a pilot study. Pol J Pathol. 2022;73(1):50–9. https://doi.org/10.5114/pjp.2022.117178.
Canavan M, Floudas A, Veale DJ, Fearon U. The PD-1:PD-L1 axis in inflammatory arthritis. BMC Rheumatol. 2021;5(1):1. https://doi.org/10.1186/s41927-020-00171-2.
Kosova IV, Loran OB, Sinyakova LA, et al. Immunohistochemical characteristics of bladder cancer in patients with virus-positive tumors. Onkourologiya. 2018;14(2):142–54. https://doi.org/10.17650/1726-9776-2018-14-2-142-154.
Nakanishi J, Wada Y, Matsumoto K, Azuma M, Kikuchi K, Ueda S. Overexpression of B7–H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol Immunother. 2007;56(8):1173–82. https://doi.org/10.1007/s00262-006-0266-z.
Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800. https://doi.org/10.1038/nm730. Erratum: 8(9):1039.
Wang Y, Zhuang Q, Zhou S, Hu Z, Lan R. Costimulatory molecule B7–H1 on the immune escape of bladder cancer and its clinical significance. J Huazhong Univ Sci Technolog Med Sci. 2009;29(1):77–9. https://doi.org/10.1007/s11596-009-0116-2.
Inman BA, Sebo TJ, Frigola X, et al. PD-L1 (B7–H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer. 2007;109(8):1499–505. https://doi.org/10.1002/cncr.22588.
Ghosh C, Luong G, Sun Y. A snapshot of the PD-1/PD-L1 pathway. J Cancer. 2021;12(9):2735–46. https://doi.org/10.7150/jca.57334.
Sun JX, Xu JZ, Liu CQ, et al. The association between human papillomavirus and bladder cancer: evidence from meta-analysis and two-sample Mendelian randomization. J Med Virol. 2023;95(1):e28208. https://doi.org/10.1002/jmv.28208.
Panagiotakis GI, Papadogianni D, Chatziioannou MN, Lasithiotaki I, Delakas D, Spandidos DA. Association of human herpes, papilloma and polyoma virus families with bladder cancer. Tumour Biol. 2013;34(1):71–9. https://doi.org/10.1007/s13277-012-0512-2.
Murata T. Human herpesvirus and the immune checkpoint PD-1/PD-L1 pathway: disorders and strategies for survival. Microorganisms. 2021;9(4):778. https://doi.org/10.3390/microorganisms9040778.
Jubel JM, Barbati ZR, Burger C, Wirtz DC, Schildberg FA. The role of PD-1 in acute and chronic infection. Front Immunol. 2020;24(11):487. https://doi.org/10.3389/fimmu.2020.00487.
Jørgensen KR, Jensen JB. Human papillomavirus and urinary bladder cancer revisited. APMIS. 2020;128(2):72–9. https://doi.org/10.1111/apm.13016.
Benedict CA, Loewendorf A, Garcia Z, Blazar BR, Janssen EM. Dendritic cell programming by cytomegalovirus stunts naive T cell responses via the PD-L1/PD-1 pathway. J Immunol. 2008;180(7):4836–47. https://doi.org/10.4049/jimmunol.180.7.4836.
Blackburn SD, Shin H, Haining WN, et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2009;10(1):29–37. https://doi.org/10.1038/ni.1679.
Nechifor-Boilă IA, Loghin A, Nechifor-Boilă A, et al. PD-L1 expression in muscle invasive urothelial carcinomas as assessed via immunohistochemistry: correlations with specific clinical and pathological features, with emphasis on prognosis after radical cystectomy. Life (Basel). 2021;11(5):404. https://doi.org/10.3390/life11050404.
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I.K.: study conception and design, data collection, revision of the manuscript; V.B.: study conception and design, data collection, analysis and interpretation of results, draft manuscript preparation; L.G.: data collection, revision of the manuscript; D.K.: data collection, revision of the manuscript. All authors read and approved the final version of the manuscript.
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The study was approved by the Local Ethics Committee of the Russian Medical Academy of Continuous Professional Education (Protocol #15, 16/11/2021) and conducted in accordance with the principles of the Helsinki Declaration. All patients signed an informed consent form before participating in the study.
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Kosova, I., Barsegian, V., Gundorova, L. et al. PD-L1 Expression in Nonbacterial Chronic Cystitis and Bladder Cancer. Int Urogynecol J (2024). https://doi.org/10.1007/s00192-024-05782-8
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DOI: https://doi.org/10.1007/s00192-024-05782-8