Infiltrating immune cells are associated with radiosensitivity and favorable survival in head and neck cancer treated with definitive radiotherapy.

Abstract

The aim of this study was to investigate the influence of CD4+, CD8+ and Forkhead box protein 3 (FoxP3+) tumor-infiltrating lymphocytes, as well as CD1a+ tumor-infiltrating dendritic cells on the radiosensitivity and survival of primarily chemoirradiated advanced head and neck squamous cell carcinomas. Immunohistochemical staining for CD4, CD8, FoxP3 and CD1a was performed in 82 primarily chemoirradiated head and neck squamous cell carcinomas. Associations with clinicopathologic data, programmed cell death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), p16, radiation response, and survival were examined. High CD4 expression was associated with complete response after radiation (P=.006) and high CD1a expression (P=.024). High CD8+ tumor-infiltrating lymphocyte counts were associated with absence of tumor relapse (P=.032) and better disease-free survival (P=.051). Strong overall T-cell infiltration was found more often in tumors with high-grade differentiation (P=.004), complete response after radiation (P=.022), and better overall survival and disease-specific survival (each P=.052). Tumors with high FoxP3+ T regulatory (Treg) infiltration more often showed high-grade tumor differentiation (P=.017), advanced patient age (P=.02), high PD-1 (P=.007), high CD4 (P=.002), and high CD8 expression (P=.002), as well as better disease-free survival (P=.019). T-cell activation (high CD4, CD8 and FoxP3 expression) is associated with radio response and favorable survival in advanced head and neck cancer treated with definitive chemoradiation.