Tumor-Infiltrating Lymphocytes in the Tumor Microenvironment of Laryngeal Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.

Juan P Rodrigo,Michelle D Williams,Fernando López,Gregory T Wolf,Andrés Coca-Pelaz,Mario Sánchez-Canteli,Alfio Ferlito,Juan C Hernández-Prera,Stefan M Willems,Alessandro Franchi

doi:10.3390/biomedicines9050486

Abstract

The presence of tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment has been demonstrated to be of prognostic value in various cancers. In this systematic review and meta-analysis, we investigated the prognostic value of TIL in laryngeal squamous cell carcinoma (LSCC). We performed a systematic search in PubMed for publications that investigated the prognostic value of TIL in LSCC. A meta-analysis was performed including all studies assessing the association between TIL counts in hematoxylin-eosin (HE)-stained sections, for CD8+ and/or CD3+/CD4+ TIL and overall survival (OS) or disease-free survival (DFS). The pooled meta-analysis showed a favorable prognostic role for stromal TIL in HE sections for OS (HR 0.57, 95% CI 0.36–0.91, p = 0.02), and for DFS (HR 0.56, 95% CI 0.34–0.94, p = 0.03). High CD8+ TIL were associated with a prolonged OS (HR 0.62, 95% CI 0.4–0.97, p = 0.04) and DFS (HR 0.73, 95% CI 0.34–0.94, p = 0.002). High CD3+/CD4+ TIL demonstrated improved OS (HR 0.32, 95% CI 0.16–0.9, p = 0.03) and DFS (HR 0.23, 95% CI 0.10–0.53, p = 0.0005). This meta-analysis confirmed the favorable prognostic significance of TIL in LSCC. High stromal TIL evaluated in HE sections and intra-tumoral and stromal CD3+, CD4+ and/or CD8+ TIL might predict a better clinical outcome.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the most frequent malignancy in the head and neck region, and the seventh most commonly diagnosed cancer [1]
The pooled meta-analysis showed an advantage for high CD4+ and/or CD3+ tumor-infiltrating lymphocytes (TIL) (pooled Hazard ratios (HRs) 0.32, p = 0.03, for overall survival (OS), and 0.23, p = 0.0005, for disease-free survival (DFS))
In this systematic review we investigated the prognostic value of TIL in the tumor microenvironment of laryngeal squamous cell carcinoma (LSCC)

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the most frequent malignancy in the head and neck region, and the seventh most commonly diagnosed cancer [1]. HNSCCs, laryngeal squamous cell carcinoma (LSCC) is the second most common location after oral cavity squamous cell carcinoma. Despite improvements in the field of surgery, chemotherapy, and radiotherapy, patients with LSCC still face an unfavorable prognosis. Effective therapeutic strategies and increased understanding of the relevant mechanisms implicated in treatment failure are needed to improve the prognosis of patients with LSCC [2]. Tumor progression and response to treatment are influenced by the interaction between tumor cells and the surrounding tumor microenvironment (TME). The TME is composed of a variety of cellular entities including fibroblasts, endothelial cells, blood vessels, lymph vessels, and cells of the immune system [3]

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