The number of intratumoral dendritic cells and zeta-chain expression in T cells as prognostic and survival biomarkers in patients with oral carcinoma.

BACKGROUND: Dendritic cells (DCs) are antigen-presenting cells with a unique ability to cross prime T cells and generate strong antitumor responses. This study evaluates the presence and prognostic significance of DCs as well as functional T cells, which accumulate in the microenvironment in patients with oral squamous cell carcinoma (OSCC).

METHODS: Immunohistochemistry for S-100 positive or p55 positive DCs and for T-cell receptor (TcR)-associated zeta-chain expression in tumor-infiltrating lymphocytes (TILs) was performed in 132 paraffin embedded specimens from patients with primary OSCC. The median clinical follow-up for the patients was 50 months. The numbers of intratumoral DCs or TILs expressing the zeta chain were determined microscopically and compared with clinical and pathohistologic prognostic parameters, including disease stage, T stage or tumor grade, lymph node involvement, as well as disease free survival and overall survival.

RESULTS: Immunostaining identified DCs in the epithelial compartment of the tumors (S-100 positive) as well as interdigitating reticular DCs (p55 positive) in peritumoral areas. Based on S-100 staining, intratumoral DC infiltrates were low (<10 DCs per high-power field [HPF]) in 20% of OSCC specimens, intermediate (10-20 DCs per HPF) in 42% of OSCC specimens, and high (>20 DCs per HPF) in 37% of OSCC specimens. The number of S-100 positive DCs was positively and significantly correlated with that of p55 and of TILs with normal zeta-chain expression. A low number of infiltrating S-100 positive DCs was more predictive of poor survival (hazard ratio, 7.95) than lymph node involvement (hazard ratio, 3.36) or late T stage (hazard ratio, 2.92). A significant but weaker association of p55 positive DC infiltration with survival was observed. Low density of DCs and low or absent expression of the zeta chain in TILs correlated with each other and predicted the poorest survival and the greatest risk.

CONCLUSIONS: The number of DCs infiltrating the tumor is a highly significant prognostic parameter in patients with OSCC. Furthermore, the absence or paucity of DCs is strongly linked to abnormalities in the TcR-associated zeta chain in TILs. The two biomarkers, zeta-chain expression in TILs and the number of S-100+ DCs in the tumor, independently predict overall survival, disease free survival, and time to disease recurrence in patients with OSCC.