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Prognostic Value of Tumor-Infiltrating Dendritic Cells in Colorectal Cancer: Role of Maturation Status and Intratumoral Localization

Authors' Affiliations: Departments of ¹ Surgery, ² Immunohematology and Blood Transfusion, and ³ Pathology, Leiden University Medical Center, Leiden, the Netherlands

Requests for reprints: Peter J.K. Kuppen, Department of Surgery, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, the Netherlands. Phone: 31-526-2309; E-mail: P.J.K.Kuppen{at}lumc.nl.

The clinical significance of tumor-infiltrating dendritic cells has been reported in a variety of human solid tumors as shown by the correlations found between the presence of tumor-infiltrating dendritic cells and clinical prognosis. In this study, we evaluated whether there is an association between the presence and maturation status of tumor-infiltrating dendritic cells, T lymphocytes, and clinical course in 104 primary tumor samples of patients with colorectal cancer. Dendritic cells were identified with four different markers (S-100, HLA class II, CD208, and CD1a) in double immunohistochemistry, with laminin as second marker to support the exact localization. Tumor-infiltrating dendritic cells showed a distinct infiltration pattern based on their maturation status. CD1a-positive dendritic cells resided in the advancing tumor margins in relatively high numbers, whereas mature CD208-positive dendritic cells were sparsely present in the tumor epithelium but mainly distributed in the tumor stroma and advancing tumor margin. Furthermore, high infiltration of CD1a-positive dendritic cells in the tumor epithelium was significantly correlated to the infiltration of CD4 lymphocytes (P = 0.006). Patients with relatively high numbers of mature CD208-positive infiltrating dendritic cells in the tumor epithelium had a shorter overall survival (P = 0.004). In addition, patients with relatively high numbers of CD1a-positive dendritic cells in the advancing margin of the tumor had a shorter disease-free survival (P = 0.03). We found that tumor-infiltrating dendritic cells had preferential infiltration sites within a tumor, affected local tumor cell-immune cell interactions, and correlated to the clinical prognosis of colorectal cancer patients.

Key Words: Antigen-presenting cells • adenocarcinoma • CD1a • CD208 • tumor-infiltrating leukocytes

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