Human dendritic cell mediated cytotoxicity against breast carcinoma cells in vitro.
Dendritic cells (DC) are an important subset of antigen-presenting cells characterized by their potent capacity to activate immunologically naïve T cells. However, their role in effector function in tumor resistance is less well characterized. We report here that activated human peripheral blood DC acquire a potent antitumor effect against breast cancer cell lines in vitro, leading to growth inhibition and apoptosis of the tumor cell. The antitumor effect of DC was augmented by proinflammatory stimuli induced by lipopolysaccharide (LPS) treatment. Tumor necrosis factor alpha (TNF-alpha) produced after DC activation was responsible for the antitumor activity of DC. Interferon-gamma, interleukin-15, or LPS treatment of DC markedly augmented the effector function of DC against most of the breast cells, indicating heterogeneity of the tumor and its susceptibility to cytokine-mediated damage. Treatment of LPS-activated DC or cell-free supernatant with anti-human TNF-alpha significantly reduces the antitumor effect against the tumor cells tested. These results suggest that in addition to their predominant role as immune regulatory cells, DC could serve as innate effector cells in tumor immunity.
Manna
Partha P
PP
Department of Surgery, Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Mohanakumar
T
T
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D002277:Carcinoma / Q000276:immunology / Q000473:pathology*; D002455:Cell Division; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D019409:Interleukin-15 / Q000235:genetics / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology
D000911:Antibodies, Monoclonal; D019409:Interleukin-15; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor