Lequerica-Fernández Paloma, Rodríguez-Santamarta Tania, García-García Eduardo, Blanco-Lorenzo Verónica, Torres-Rivas Héctor E, Rodrigo Juan P, Suárez-Sánchez Faustino J, García-Pedrero Juana M, De Vicente Juan Carlos
Department of Biochemistry, Hospital Universitario Central de Asturias (HUCA), Carretera de Rubín, 33011 Oviedo, Spain.
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Carretera de Rubín, 33011 Oviedo, Spain.
Biomedicines. 2023 Sep 29;11(10):2675. doi: 10.3390/biomedicines11102675.
The aim of this study was to investigate the prognostic relevance of β-catenin expression in oral squamous cell carcinoma (OSCC) and to explore relationships with the tumor immune microenvironment. Expression of β-catenin and PD-L1, as well as lymphocyte and macrophage densities, were evaluated by immunohistochemistry in 125 OSCC patient specimens. Membranous β-catenin expression was detected in 102 (81.6%) and nuclear β-catenin in 2 (1.6%) tumors. There was an association between β-catenin expression, tumoral, and stromal CD8 T-cell infiltration (TIL) and also the type of tumor immune microenvironment (TIME). Tumors harboring nuclear β-catenin were associated with a type II TIME (i.e., immune ignorance defined by a negative PD-L1 expression and low CD8 TIL density), whereas tumors with membranous β-catenin expression were predominantly type IV (i.e., immune tolerance defined by negative PD-L1 and high CD8 TIL density). Combined, but not individual, high stromal CD8 TILs and membranous β-catenin expression was independently associated with better disease-specific survival (HR = 0.48, = 0.019). Taken together, a combination of high stromal CD8 T-cell infiltration and membranous β-catenin in the tumor emerges as an independent predictor of better survival in OSCC patients.
本研究旨在探讨β-连环蛋白表达在口腔鳞状细胞癌（OSCC）中的预后相关性，并探索其与肿瘤免疫微环境的关系。通过免疫组织化学方法评估了125例OSCC患者标本中β-连环蛋白和PD-L1的表达，以及淋巴细胞和巨噬细胞密度。在102例（81.6%）肿瘤中检测到膜性β-连环蛋白表达，2例（1.6%）肿瘤中检测到核β-连环蛋白表达。β-连环蛋白表达、肿瘤及基质CD8 T细胞浸润（TIL）之间存在关联，同时也与肿瘤免疫微环境（TIME）类型有关。核β-连环蛋白阳性的肿瘤与II型TIME相关（即由阴性PD-L1表达和低CD8 TIL密度定义的免疫忽视），而膜性β-连环蛋白表达阳性的肿瘤主要为IV型（即由阴性PD-L1和高CD8 TIL密度定义的免疫耐受）。基质CD8 TILs高表达与膜性β-连环蛋白表达联合（而非单独）与更好的疾病特异性生存独立相关（HR = 0.48， = 0.019）。综上所述,肿瘤中基质CD8 T细胞浸润高表达与膜性β-连环蛋白联合出现是OSCC患者更好生存的独立预测指标。
