Expression of tumoral GSK3-β, PD-L1, and CD8 cell density in urothelial carcinomas, association with tumor grade and overall survival.

IF 1.4 Q4 IMMUNOLOGY American journal of clinical and experimental immunology Pub Date : 2023-10-15 eCollection Date: 2023-01-01
Aline Kimberly Almeida Rodrigues, Paulo Goberlanio Silva, Cleto Nogueira, Samuel S Ferreira, Juliana Cordeiro, Benedito Carneiro, Fabio Tavora
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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.

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尿路上皮癌中肿瘤GSK3-β、PD-L1和CD8细胞密度的表达与肿瘤分级和总生存期的关系
膀胱癌是泌尿道中最常见的恶性肿瘤,在生物学和临床上具有很大的异质性。大约90%的诊断是在60年代做出的,在男性中更为普遍。程序性细胞死亡1 (PD-1)和程序性细胞死亡配体1 (PD-L1)轴被认为在免疫检查点中起作用,并且是癌症逃避免疫系统的一种手段。glicogênio合成酶激酶(GSK) 3的抑制通过上调转录因子Tbet导致PD-1的下调。生物标志物PD-L1和GSK-3β的使用以及免疫浸润的评估与尿路上皮癌的预后和治疗预测有很好的相关性。目的:探讨膀胱癌组织中PD-L1、GSK-3β蛋白表达与cd8阳性免疫浸润的关系。材料和方法:这是一项对2015年至2018年140例尿路上皮癌样本的横断面研究。由两名病理学家独立评估GSK-3β (27C10)、CD8 (7103β)和PDL-1 (22c3)标记物的自动数字辅助评分和常规分析,并计算组织学评分。同时测定CD8的密度。结果:大多数标本中有91%的GSK-3β、62.9%的PD-L1和46.3%的CD8细胞的免疫表达。结论:尽管肿瘤微环境存在异质性,但CD8、GSK-3β和PDL1的表达可能是有价值的,GSK-3β可能是晚期膀胱癌的潜在靶点,特别是在免疫治疗的背景下。
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