Bioinformatics analysis for the biomarkers of the tumor-infiltrating lymphocytes in head and neck squamous cell carcinoma

Background: Immunotherapy strategies are successful in only a subset of patients with advanced head and neck squamous cell carcinoma (HNSCC). The roles of tumor-infiltrating lymphocytes (TILs) in HNSCC are less clear. Herein, we present a preliminary study to identify the underlying heterogeneity and correlations among TILs in HNSCC by bioinformatics analysis of TIL-related biomarkers. Methods: The expression patterns, clinicopathological values and underlying correlations for the TILs related genes were analyzed based on the TCGA primary HNSCC cohort. The prognostic significance for the involved genes in the HNSCC patients was evaluated by using an online tool, Kaplan-Meier Plotter. Bioinformatics prediction for the co-expression, physical interactions, pathway, and genetic interactions of the involved genes was performed by using GeneMANIA. Results: The expression of programmed death-ligand 1 (PD-L1) was significantly correlated with the expression of CD4 (P<0.01), CD8 (P<0.01), and CD20 (P=0.011), but not CD56 (P=0.065) based on the TCGA primary HNSCC cohort. For the expression of programmed cell death 1 (PD-1), a significant correlation was also observed with the expression of CD4 (P<0.01), CD8 (P<0.01), and CD20 (P<0.01), but not CD56 (P=0.861). For the clinically significant evaluation, variable roles for the biomarkers were compared and demonstrated. Increased expression of CD8 (P=0.029), CD20 (P<0.01), or PD-1 (P=0.0084) significantly correlated with improved overall survival (OS), and increased CD56 expression indicated obviously decreased OS for HNSCC patients (P=0.0033). Significantly positive correlations between human papilloma virus (HPV) status and the expression of CD8 (P<0.01), CD20 (P<0.01) and PD-1 (P<0.01) were demonstrated and a significantly negative correlation between HPV status and CD56 expression was also demonstrated (P<0.01). In addition, IL2RB was determined to be a hub factor that regulates the infiltration of TILs and the expression of PD-1/PD-L1 in HNSCC. Conclusions: A systematic evaluation for the TILs status can be informative to predict prognosis and direct the immunotherapy for HNSCC patients, but further investigations are still needed.