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RESEARCH PRODUCT

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

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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 ζ-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 ζ 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 ( 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 ζ-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 ζ 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 ζ chain in TILs. The two biomarkers, ζ-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. Cancer 2001;91:2136–47. © 2001 American Cancer Society.