Lequerica-Fernández Paloma, Suárez-Canto Julián, Rodriguez-Santamarta Tania, Rodrigo Juan Pablo, Suárez-Sánchez Faustino Julián, Blanco-Lorenzo Verónica, Domínguez-Iglesias Francisco, García-Pedrero Juana María, de Vicente Juan Carlos
Department of Biochemistry, Hospital Universitario Central de Asturias (HUCA), C/Carretera de Rubín, s/n, 33011 Oviedo, Spain.
Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, C/Carretera de Rubín, s/n, 33011 Oviedo, Spain.
Biomedicines. 2021 Jun 8;9(6):653. doi: 10.3390/biomedicines9060653.
This study investigates the relevance of tumor-infiltrating lymphocytes (TILs) in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis of stromal/tumoral CD4, CD8 and FOXP3 TILs is performed in 125 OSCC patients. Potential relationships with the expression of tumoral PD-L1 and cancer stem cell (CSC) markers (NANOG, SOX2, OCT4, Nestin and Podoplanin (PDPN)) are assessed. CD4 and CD8 TILs are significantly associated with smoking and alcohol habits. CD4 and CD8 TILs show an inverse relationship with NANOG and SOX2 expression, and FOXP3 TILs is significantly correlated with Nestin and PDPN expression. High infiltration of CD4 and CD8 TILs and a high tumoral CD8/FOXP3 ratio are significantly associated with tumors harboring positive PD-L1 expression. Infiltration of stromal/tumoral FOXP3 TILs and a low stromal CD8/FOXP3 ratio are significantly associated with better disease-specific survival. Multivariate analysis reveals that the stromal CD8/FOXP3 TILs ratio is a significant independent prognostic factor. Regarding OSCC patient survival, the CD8/FOXP3 TILs ratio is an independent prognostic factor. TILs may act as biomarkers and potential therapeutic targets for OSCC.
本研究调查肿瘤浸润淋巴细胞(TILs)在口腔鳞状细胞癌(OSCC)中的相关性。对125例OSCC患者进行基质/肿瘤CD4、CD8和FOXP3 TILs的免疫组织化学分析。评估其与肿瘤PD-L1表达及癌症干细胞(CSC)标志物(NANOG、SOX2、OCT4、巢蛋白和血小板内皮细胞黏附分子(PDPN))表达的潜在关系。CD4和CD8 TILs与吸烟和饮酒习惯显著相关。CD4和CD8 TILs与NANOG和SOX2表达呈负相关,而FOXP3 TILs与巢蛋白和PDPN表达显著相关。CD4和CD8 TILs的高浸润以及肿瘤CD8/FOXP3高比值与PD-L1表达阳性的肿瘤显著相关。基质/肿瘤FOXP3 TILs的浸润以及基质CD8/FOXP3低比值与更好的疾病特异性生存显著相关。多变量分析显示,基质CD8/FOXP3 TILs比值是一个显著的独立预后因素。关于OSCC患者的生存,CD8/FOXP3 TILs比值是一个独立的预后因素。TILs可能作为OSCC的生物标志物和潜在治疗靶点。