title: Dendritic cells in colorectal cancer correlate with other tumor-infiltrating immune cells.
abstract: Dendritic cells (DCs) are the most efficient antigen-presenting cells and play a key role in a cellular antitumor immune response. In this study we investigated the exact localization of DCs within colorectal tumors and their relationship to tumor-infiltrating lymphocytes as well as clinical outcome of the patients. Primary tumor specimens of 104 patients with a diagnosis of colorectal cancer were identified retrospectively and analyzed with the dendritic cell markers S-100 protein and human leukocyte antigens (HLA) class II. The markers were individually combined with laminin as a second marker to facilitate the observation of the different tumor localizations. S-100 or HLA class II positive cells were found in the three different compartments of colorectal tumors: tumor epithelium, tumor stroma, and advancing tumor margin, but mainly present in tumor stroma and advancing tumor margin. S-100-positive tumor-infiltrating DCs in direct contact with tumor cells, i.e., in tumor epithelium, significantly correlated to the intraepithelial infiltration of CD4+ (p=0.02) and CD8+ (p=0.01) lymphocytes. High HLA class II+ cell infiltration in the tumor stroma correlated to a lower intraepithelial infiltration of CD8+ (p=0.02) lymphocytes. High intraepithelial infiltration of S-100-positive DCs suggested increased disease-free survival, but was not statistically significant, while high amounts of HLA class II+ cells in the tumor stroma correlated with an adverse survival outcome. Our results show that the infiltration of DCs in colorectal cancer, depending on both location and type of marker, is correlated with local immune interactions and patient prognosis, suggesting a central role for DCs in controlling local tumor immunity.
authors.affiliation: Department of Surgery, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: A R
authors.initials: AR
authors.lastname: Dadabayev
authors.forename: M H
authors.initials: MH
authors.lastname: Sandel
authors.forename: A G
authors.initials: AG
authors.lastname: Menon
authors.forename: H
authors.initials: H
authors.lastname: Morreau
authors.forename: C J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: R
authors.initials: R
authors.lastname: Offringa
authors.forename: S H
authors.initials: SH
authors.lastname: van der Burg
authors.forename: C
authors.initials: C
authors.lastname: Janssen-van Rhijn
authors.forename: N G
authors.initials: NG
authors.lastname: Ensink
authors.forename: R A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: P J K
authors.initials: PJ
authors.lastname: Kuppen
mesh_terms: D000328:Adult; D000368:Aged; D000938:Antigen-Presenting Cells / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018572:Disease-Free Survival; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D000949:Histocompatibility Antigens Class II / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000737:chemistry; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D009418:S100 Proteins / Q000096:biosynthesis* / Q000737:chemistry; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000949:Histocompatibility Antigens Class II; D007797:Laminin; D009418:S100 Proteins