Aline Kimberly Almeida Rodrigues, Paulo Goberlanio Silva, Cleto Nogueira, Samuel S Ferreira, Juliana Cordeiro, Benedito Carneiro, Fabio Tavora
{"title":"Expression of tumoral GSK3-β, PD-L1, and CD8 cell density in urothelial carcinomas, association with tumor grade and overall survival.","authors":"Aline Kimberly Almeida Rodrigues, Paulo Goberlanio Silva, Cleto Nogueira, Samuel S Ferreira, Juliana Cordeiro, Benedito Carneiro, Fabio Tavora","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Bladder cancer is the most common malignancy in the urinary tract, and is biologically and clinically quite heterogeneous. Around 90% of diagnoses are made in the 6<sup>th</sup> decade, being more prevalent in males. The programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) axis play a putative role in immune checkpoint and as a means through which cancer evades the immune system. Inhibition of the glicogênio synthase kinase (GSK) 3 leads to the downregulation of PD-1 via upregulation of the transcription factor Tbet. The use of biomarkers PD-L1 and GSK-3β and evaluation of the immune infiltrate have very promising correlations with urothelial carcinoma prognosis and treatment prediction.</p><p><strong>Objective: </strong>To investigate the protein expression of PD-L1 and GSK-3β and the CD8-positive immune infiltrates in bladder carcinomas.</p><p><strong>Materials and methods: </strong>This was a cross-sectional study of 140 samples of urothelial carcinomas from 2015 to 2018. Automated digitally assisted scoring and conventional analyses of the markers of GSK-3β (27C10), CD8 (7103β) and PDL-1 (22c3), were reviewed by two pathologists independently and a histologic score was calculated. The density of CD8 was also measured.</p><p><strong>Results: </strong>The immunoexpression of GSK-3β (91%) was presented in most samples, PD-L1 in 62.9% and CD8 cells present in 46.3% of cases. When analyzed in conjunction, the levels of GSK-3β and PD-L1 (P = 0.033), and CD8 and PD-L1 (P<0.002) showed significant correlations. No significant associations were observed between GSK-3β and CD8. The positivity of GSK-3β and PD-L1 was predominant in high-grade tumors.</p><p><strong>Conclusion: </strong>Despite the tumor microenvironment heterogeneity, the expression of CD8, GSK-3β and PDL1 could be valuable and GSK-3β could be a potential target in advanced bladder cancer, especially in the context of immunotherapy.</p>","PeriodicalId":72163,"journal":{"name":"American journal of clinical and experimental immunology","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658161/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of clinical and experimental immunology","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Bladder cancer is the most common malignancy in the urinary tract, and is biologically and clinically quite heterogeneous. Around 90% of diagnoses are made in the 6th decade, being more prevalent in males. The programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) axis play a putative role in immune checkpoint and as a means through which cancer evades the immune system. Inhibition of the glicogênio synthase kinase (GSK) 3 leads to the downregulation of PD-1 via upregulation of the transcription factor Tbet. The use of biomarkers PD-L1 and GSK-3β and evaluation of the immune infiltrate have very promising correlations with urothelial carcinoma prognosis and treatment prediction.
Objective: To investigate the protein expression of PD-L1 and GSK-3β and the CD8-positive immune infiltrates in bladder carcinomas.
Materials and methods: This was a cross-sectional study of 140 samples of urothelial carcinomas from 2015 to 2018. Automated digitally assisted scoring and conventional analyses of the markers of GSK-3β (27C10), CD8 (7103β) and PDL-1 (22c3), were reviewed by two pathologists independently and a histologic score was calculated. The density of CD8 was also measured.
Results: The immunoexpression of GSK-3β (91%) was presented in most samples, PD-L1 in 62.9% and CD8 cells present in 46.3% of cases. When analyzed in conjunction, the levels of GSK-3β and PD-L1 (P = 0.033), and CD8 and PD-L1 (P<0.002) showed significant correlations. No significant associations were observed between GSK-3β and CD8. The positivity of GSK-3β and PD-L1 was predominant in high-grade tumors.
Conclusion: Despite the tumor microenvironment heterogeneity, the expression of CD8, GSK-3β and PDL1 could be valuable and GSK-3β could be a potential target in advanced bladder cancer, especially in the context of immunotherapy.