Abstract
T lymphocyte survival is critical for the development and maintenance of an effective host antitumor immune response; however, the tumor environment can negatively impact T-cell survival. Lymphocytes exposed to tumor supernatants (TSNs) were evaluated for apoptosis after mitogen stimulation. TSN was observed to significantly enhance phorbol 12-myristate 13-acetate/ionomycin- and anti-CD3-stimulated lymphocyte apoptosis. Enhanced lymphocyte apoptosis was associated with an impairment of nuclear factor kappa B nuclear translocation and diminished I kappa B alpha degradation. In lymphocytes stimulated after exposure to TSNs, cytoplasmic I kappa B alpha persisted as a result of alterations in I kappa B kinase (IKK) activity. Accordingly, although there were no apparent differences in IKK component concentrations, lymphocytes preexposed to TSNs exhibited markedly reduced IKK activity. We conclude that non-small cell lung cancer-derived soluble factors promote apoptosis in activated lymphocytes by an IKK-dependent pathway.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma / enzymology
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Adenocarcinoma / immunology
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Apoptosis / immunology*
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CD3 Complex / immunology
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Carcinoma, Non-Small-Cell Lung / enzymology
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Carcinoma, Non-Small-Cell Lung / immunology*
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / pathology
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Humans
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I-kappa B Kinase
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I-kappa B Proteins / immunology
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I-kappa B Proteins / metabolism
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Ionomycin / pharmacology
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Jurkat Cells / enzymology
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Jurkat Cells / immunology
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Jurkat Cells / pathology
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Lung Neoplasms / enzymology
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Lung Neoplasms / immunology*
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Lung Neoplasms / metabolism
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Lung Neoplasms / pathology
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NF-kappa B / immunology
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NF-kappa B / metabolism
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Protein Serine-Threonine Kinases / immunology*
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Protein Serine-Threonine Kinases / metabolism
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T-Lymphocytes / enzymology
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T-Lymphocytes / immunology*
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T-Lymphocytes / pathology
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Tetradecanoylphorbol Acetate / pharmacology
Substances
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CD3 Complex
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I kappa B beta protein
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I-kappa B Proteins
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NF-kappa B
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Ionomycin
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Protein Serine-Threonine Kinases
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CHUK protein, human
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I-kappa B Kinase
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IKBKB protein, human
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IKBKE protein, human
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Tetradecanoylphorbol Acetate