title: Induction of tolerogenic dendritic cells by IL-6-secreting CT26 colon carcinoma.
abstract: One scenario by which tumors escape immune recognition is the constitutive activation of signal transducer and activator of transcription 3 (STAT3). This transcription factor mediates the production of tumor-derived factors that negatively influence target immune cells, such as dendritic cells, and polarize them toward immune-tolerance also through the induction of STAT3 activation. In the current study, the effect of p-STAT3-positive murine colon carcinoma cell line (CT26) on bone marrow-derived DCs was examined. The results showed a remarkable increase in p-STAT3 in dendritic cells (DCs) only after CT26-CM incubation. The induction of p-STAT3 in CT26-CM exposed DCs was attributed at least in part to the high levels of interleukin-6 secreted by CT26 in culture. This was also accompanied by a significant reduction in the response to the immunostimulatory adjuvant lipopolysaccharide by lowering the expression of co-stimulatory molecules CD86 and CD40. Taken together, the results suggest an inhibitory effect of CT26 colon carcinoma on DC maturation through induction of STAT3 phosphorylation. Therefore, tumor-induced p-STAT3 in DCs can be seen as a promising target for colon cancer immunotherapy.
authors: Nanomedicine Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. aalshamsan@ksu.edu.sa
authors: Aws
authors: A
authors: Alshamsan
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007108:Immune Tolerance; D007167:Immunotherapy; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D015850:Interleukin-6; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse