Role of tumor cell apoptosis in tumor antigen migration to the draining lymph nodes.
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.
Bonnotte
B
B
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
Favre
N
N
Moutet
M
M
Fromentin
A
A
Solary
E
E
Martin
M
M
Martin
F
F
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
D000951:Antigens, Neoplasm; D009363:Neoplasm Proteins; D016650:Fluorescein-5-isothiocyanate