title: Prognostic value of tumor-infiltrating dendritic cells in colorectal cancer: role of maturation status and intratumoral localization.
abstract: 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.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Maro H
authors.initials: MH
authors.lastname: Sandel
authors.forename: Alisher R
authors.initials: AR
authors.lastname: Dadabayev
authors.forename: Anand G
authors.initials: AG
authors.lastname: Menon
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Rienk
authors.initials: R
authors.lastname: Offringa
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
authors.forename: Connie M
authors.initials: CM
authors.lastname: Janssen-van Rhijn
authors.forename: N Geeske
authors.initials: NG
authors.lastname: Ensink
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D003713:Dendritic Cells / Q000737:chemistry / Q000473:pathology*; D004848:Epithelium / Q000737:chemistry / Q000473:pathology; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D051907:Lysosomal Membrane Proteins; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D009418:S100 Proteins / Q000032:analysis; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; C419393:CD1a antigen; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D051907:Lysosomal Membrane Proteins; D009418:S100 Proteins