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

Abstract

Objectives: 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.

Study design: 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.

Results: 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 (T_reg) 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).

Conclusions: 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.