The prognostic role of tumor infiltrating T-lymphocytes in squamous cell carcinoma of the head and neck: A systematic review and meta-analysis

Emma J de Ruiter, Marc L Ooft, Lot A Devriese, Stefan M Willems, Emma J de Ruiter, Marc L Ooft, Lot A Devriese, Stefan M Willems

Abstract

Background - The presence of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment is associated with an improved prognosis and a better response to therapy in different types of cancer. In this systematic review and meta-analysis, we investigated the prognostic value of T cells in head and neck squamous cell carcinoma (HNSCC). Methods - In a systematic review, Pubmed and Embase were searched for publications that investigated the prognostic value of T cells in HNSCC. A meta-analysis was performed including all studies assessing the association between CD3+, CD4+, CD8+, and FoxP3+ TILs and overall survival (OS), disease-free survival (DFS), or locoregional control (LRC). Results - A pooled analysis indicated a favorable, prognostic role for CD3+ TILs (HR 0.64 (95%CI 0.47-0.85) for OS, HR 0.63 (95%CI 0.49-0.82) for DFS) and CD8+ TILs (HR 0.67 (95%CI 0.58-0.79) for OS, HR 0.50 (95%CI 0.37-0.68) for DFS, and HR 0.82 (95%CI 0.70-0.96) for LRC) in the clinical outcome of HNSCC. FoxP3+ TILs were also associated with better OS (HR 0.80 (95%CI 0.70-0.92)). Conclusion - This systematic review and meta-analysis confirmed the favorable, prognostic role of CD3+ and CD8+ T cell infiltration in HNSCC patients and found an association between FoxP3+ TILs and improved overall survival. Future studies using homogeneous patient cohorts with regard to tumor subsite, stage and treatment are necessary to provide more insight in the predictive value of TILs in HNSCC.

Keywords: T cells; head and neck squamous cell carcinoma (HNSCC); prognostic biomarkers; systematic review; tumor infiltrating lymphocytes (TILs).

Figures

Figure 1.
Figure 1.
Selection process. Of the 122 articles that remained after the initial title/abstract screening, 28 remained for inclusion.
Figure 2.
Figure 2.
Forest plots of prognostic value of CD3+ TILs on overall survival, disease-free survival and locoregional control in HPV-negative patients (A) and HPV-positive patients (B). No data were available for disease-free survival in HPV-positive patients.
Figure 3.
Figure 3.
Forest plots of prognostic value of CD4+ TILs on overall survival, disease-free survival and locoregional control in HPV-negative patients (A) and HPV-positive patients (B). No data were available for disease-free survival in HPV-positive patients.
Figure 4.
Figure 4.
Forest plots of prognostic value of CD8+ TILs on overall survival, disease-free survival and locoregional control in HPV-negative patients (A) and HPV-positive patients (B).
Figure 5.
Figure 5.
Forest plots of prognostic value of FoxP3+ TILs on overall survival, disease-free survival and locoregional control in HPV-negative patients (A) and HPV-positive patients (B).

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