Prognostic implications of preoperative systemic inflammatory markers in oral squamous cell carcinoma, and correlations with the local immune tumor microenvironment

Marta Ruiz-Ranz; Paloma Lequerica-Fernández; Tania Rodríguez-Santamarta; Faustino J Suárez-Sánchez; Rosa M López-Pintor; Juana M García-Pedrero; Juan C de Vicente

doi:10.3389/fimmu.2022.941351

Prognostic implications of preoperative systemic inflammatory markers in oral squamous cell carcinoma, and correlations with the local immune tumor microenvironment

Front Immunol. 2022 Jul 26:13:941351. doi: 10.3389/fimmu.2022.941351. eCollection 2022.

Authors

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
² Department of Biochemistry, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
³ Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Spain.
⁴ Department of Pathology. Hospital Universitario de Cabueñes, Gijón, Spain.
⁵ ORALMED Research Group, Department of Dental Clinical Specialties, School of Dentistry, Complutense University, Madrid, Spain.
⁶ Department of Otolaryngology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
⁷ Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.
⁸ Department of Surgery, University of Oviedo, Oviedo, Spain.

Abstract

Purpose: The aim of this study was to investigate the prognostic significance of preoperative inflammatory markers in peripheral blood of patients with oral squamous cell carcinoma (OSCC), and to establish correlations with the infiltrate of macrophages and lymphocytes in the local immune tumor microenvironment (TME).

Materials and methods: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and systemic immune-inflammation index (SII) were retrospectively evaluated in a cohort of 348 OSCC patients, and correlated with overall (OS) and disease-specific survival (DSS). Immunohistochemical analysis of tumoral and stromal infiltration of CD8+, CD4+, FOXP3+ and CD20+ lymphocytes and CD68+ and CD163+ macrophages was performed in a subset of 119 OSCC patient samples, and correlations further assessed.

Results: NLR, SII, and LMR were significantly associated with a poorer OS in univariate analysis; however, only NLR remained a significant independent predictor in the multivariate analysis (HR = 1.626, p = 0.04). NLR and SII were inversely and significantly correlated with stromal infiltration of CD8+, CD4+, and CD20+ lymphocytes. Moreover, a significant correlation between LMR was also found to significantly associate with stromal infiltration of CD8+, CD4+, and CD20+ lymphocytes, stromal CD68+ and CD163+ macrophages, and also tumoral infiltration of CD4+ and CD20+ lymphocytes.

Conclusions: Preoperative NLR, SII, and LMR may serve as valuable systemic markers to predict OSCC patient survival, with NLR emerging as an independent predictor of poor OS. Moreover, strong significant correlations were exclusively observed between systemic inflammatory markers and the local stromal infiltration of lymphocytes in the TME.

Keywords: LMR; NLR; PLR; oral cancer; prognosis; systemic immune-inflammation index; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Carcinoma, Squamous Cell* / surgery
Head and Neck Neoplasms*
Humans
Inflammation
Mouth Neoplasms* / surgery
Prognosis
Retrospective Studies
Squamous Cell Carcinoma of Head and Neck
Tumor Microenvironment

Substances

Biomarkers