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

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.

Immune Cell and Biochemical Biomarkers in Advanced Laryngeal Cancer

“…17 Previous studies showed a prognostic favorable role for several subtypes of tumor-infiltrating T cells, especially CD4 and CD8. 5,6,18 In our study, higher expression of CD4 + and CD8 + TILs were significant prognostic factors with positive impact on both OS and DSS in univariate analysis, but not in multivariate analysis. High tumoral and peritumoral density of CD4 and CD8 was identified as a positive predictor of OS, DSS, and disease free survival (DFS) in other studies as well.…”

The Exosomal miR-1246 of Laryngeal Squamous Cell Carcinoma Induces Polarization of M2 Type Macrophages and Promotes the Invasiveness of Laryngeal Squamous Cell Carcinoma

“…TME is a complex ecosystem and an active participant in all stages of LSCC occurrence and development [20]. TME is composed of many cell types, which can regulate too many cell-cell interactions, further playing a significant impact on cancer development, progression, and treatment [21].…”

“…TME is a complex ecosystem and an active participant in all stages of LSCC occurrence and development [ 20 ]. TME is composed of many cell types, which can regulate too many cell-cell interactions, further playing a significant impact on cancer development, progression, and treatment [ 21 ]. As one cell type with abundant stromal in TME, macrophages are highly plastic and can be activated into M1 or M2 polarization by stimulation of different chemokines and cytokines from TME [ 22 ].…”

MicroRNAs: Their Role in Metabolism, Tumor Microenvironment, and Therapeutic Implications in Head and Neck Squamous Cell Carcinoma

“…TILs are considered the most crucial effectors to protect against tumor development in the TME [87]. Importantly, several studies have recognized TILs as an important biomarker and a favorable prognostic factor for treatment and clinical outcomes of HNSCC [88,89]. The major components of TILs are T lymphocytes, including cytotoxic T lymphocytes (CD8+ T cells), and helper T lymphocytes (CD4+ T cells), which play a role in tumor elimination [90,91].…”