title: Role of tumor cell apoptosis in tumor antigen migration to the draining lymph nodes.
abstract: Establishment of an immune response against cancer may depend on the capacity of dendritic cells to transfer tumor Ags into T cell-rich areas. To check this possibility, we used a colon cancer cell variant that yields tumors undergoing complete T cell-dependent rejection when injected into syngeneic rats. We previously demonstrated that immunogenicity of these tumors depended on the early apoptosis of a part of these tumor cells. In this paper we show that fluorescent tumor cell proteins are released from FITC-labeled tumor cells and undergo engulfment by tumor-infiltrating monocytes without a phenotype of mature dendritic cells or macrophages. Fluorescence-labeled mononuclear cells with a phenotype of MHC class II+ dendritic cells are also found in the T cell areas of the draining lymph nodes. Interestingly, no fluorescent cell can be found in lymph nodes after a s.c. injection of Bcl2-transfected apoptosis-resistant tumor cells that yielded progressive tumors. Proliferation of tumor-immune T lymphocytes was induced by dendritic cells isolated from the draining lymph nodes recovered after a s.c. injection of apoptosis-sensitive, but not apoptosis-resistant, tumor cells. These results show that tumor cell apoptosis releases proteins that are engulfed by inflammatory cells in the tumor, then transported to lymph node T cell areas where they can induce a specific immune response leading to tumor rejection.
authors.affiliation: Department of Biology, Institut National de la Santé et de la Recherche Médicale U 517, Faculty of Medicine and Pharmacy, Dijon, France. Bernard.Bonnotte@ubourgogne.fr
authors.forename: B
authors.initials: B
authors.lastname: Bonnotte
authors.forename: N
authors.initials: N
authors.lastname: Favre
authors.forename: M
authors.initials: M
authors.lastname: Moutet
authors.forename: A
authors.initials: A
authors.lastname: Fromentin
authors.forename: E
authors.initials: E
authors.lastname: Solary
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.forename: F
authors.initials: F
authors.lastname: Martin
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D009363:Neoplasm Proteins; D016650:Fluorescein-5-isothiocyanate