Non-small cell lung cancer-derived soluble mediators enhance apoptosis in activated T lymphocytes through an I kappa B kinase-dependent mechanism.
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.
Batra
Raj K
RK
Department of Medicine and The Lung Cancer Research Program, Jonsson Comprehensive Cancer Center, University of California at Los Angeles and Veterans Administration-Greater Los Angeles Health Care System, Los Angeles, California 90095, USA.
Lin
Ying
Y
Sharma
Sherven
S
Dohadwala
Mariam
M
Luo
Jie
J
Pold
Mehis
M
Dubinett
Steven M
SM
D000230:Adenocarcinoma / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins / Q000276:immunology / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D019169:Jurkat Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017252:CD3 Complex; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D015759:Ionomycin; D017346:Protein Serine-Threonine Kinases; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human; C496565:IKBKE protein, human; D013755:Tetradecanoylphorbol Acetate