Prognostic Relevance of CD4+, CD8+ and FOXP3+ TILs in Oral Squamous Cell Carcinoma and Correlations with PD-L1 and Cancer Stem Cell Markers

Paloma Lequerica-Fernández; Julián Suárez-Canto; Tania Rodriguez-Santamarta; Juan Pablo Rodrigo; Faustino Julián Suárez-Sánchez; Verónica Blanco-Lorenzo; Francisco Domínguez-Iglesias; Juana María García-Pedrero; Juan Carlos de Vicente

doi:10.3390/biomedicines9060653

Biomedicines (Jun 2021)

Prognostic Relevance of CD4+, CD8+ and FOXP3+ TILs in Oral Squamous Cell Carcinoma and Correlations with PD-L1 and Cancer Stem Cell Markers

Paloma Lequerica-Fernández,
Julián Suárez-Canto,
Tania Rodriguez-Santamarta,
Juan Pablo Rodrigo,
Faustino Julián Suárez-Sánchez,
Verónica Blanco-Lorenzo,
Francisco Domínguez-Iglesias,
Juana María García-Pedrero,
Juan Carlos de Vicente

Affiliations

Paloma Lequerica-Fernández: Department of Biochemistry, Hospital Universitario Central de Asturias (HUCA), C/Carretera de Rubín, s/n, 33011 Oviedo, Spain
Julián Suárez-Canto: Department of Pathology, Hospital Universitario de Cabueñes, 33394 Gijón, Spain
Tania Rodriguez-Santamarta: 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
Juan Pablo Rodrigo: 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
Faustino Julián Suárez-Sánchez: Department of Biochemistry, Hospital Universitario Central de Asturias (HUCA), C/Carretera de Rubín, s/n, 33011 Oviedo, Spain
Verónica Blanco-Lorenzo: Department of Pathology, Hospital Universitario Central de Asturias (HUCA), C/Carretera de Rubín, s/n, 33011 Oviedo, Spain
Francisco Domínguez-Iglesias: Department of Biochemistry, Hospital Universitario Central de Asturias (HUCA), C/Carretera de Rubín, s/n, 33011 Oviedo, Spain
Juana María García-Pedrero: 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
Juan Carlos de Vicente: 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

DOI: https://doi.org/10.3390/biomedicines9060653
Journal volume & issue: Vol. 9, no. 6
p. 653

Abstract

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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.

Published in Biomedicines

ISSN: 2227-9059 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/biomedicines

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