Influencing Factors and Prognostic Significance of TIL Subset Abundance in Head and Neck Squamous Cell Carcinoma

Abstract

Objective: To evaluate the abundance of Foxp3-positive tumor-infiltrating lymphocytes (Foxp3+TILs), CD103+cells, CD8+TILs, and CD3+TILs in tissue specimens of 85 head and neck squamous cell carcinoma (HNSCC) and analyze the associations of their abundance with the clinicopathological features and prognosis.Methods: Immunohistochemistry was performed to detect the abundance of immunocyte subsets. Both correlation analysis and multivariate logistic regression analysis were used to analyze the associations between the frequency of these cell subsets and clinicopathological features in HNSCC. Kaplan–Meier analysis and the Cox proportional-hazards model were utilized to evaluate the effects of these immunocytes on the prognosis of patients with HNSCC.Result: Multivariate logistic regression analysis showed that an independent association of Foxp3+TILs abundance with preoperative chemotherapy (PC) was negative (P=0.018), and that with smoking index (P=0.001) and N stage (P=0.012) was positive. Multivariate Cox model revealed that the high abundance of Foxp3+TILs was independently associated with short recurrence-free survival (RFS) (P=0.015) and poor overall survival (OS) (P=0.015). The high frequency of CD103+cells was independently related to long RFS (P=0.001) and favorable OS (P<0.001). The population with a high abundance of CD8+TILs and CD103+immunocytes in HNSCC tissues exhibited optimal RFS and OS, while the sub-group with a low frequency of CD8+TILs and CD103+immunocytes showed poor RFS and OS. Moreover, Spearman’s correlation analysis revealed that the frequency of CD103+cells was positively correlated to the abundance of CD8+TILs in HNSCC (P<0.001).Conclusion: Chemotherapy eliminates the frequency of Foxp3+TILs and improves the immune tumor microenvironment (iTME) of HNSCC. On the other hand, heavy smoking upregulates the abundance of Foxp3+TILs in HNSCC tissues and disrupt the balance of immune homeostasis in iTME. Additionally, both Foxp3+TILs and CD103+cells might be potential independent prognostic indicators of HNSCC.