Non-small cell lung cancer-derived soluble mediators enhance apoptosis in activated T lymphocytes through an I kappa B kinase-dependent mechanism

Cancer Res. 2003 Feb 1;63(3):642-6.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Apoptosis / immunology*
  • CD3 Complex / immunology
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Humans
  • I-kappa B Kinase
  • I-kappa B Proteins / immunology
  • I-kappa B Proteins / metabolism
  • Ionomycin / pharmacology
  • Jurkat Cells / enzymology
  • Jurkat Cells / immunology
  • Jurkat Cells / pathology
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Protein Serine-Threonine Kinases / immunology*
  • Protein Serine-Threonine Kinases / metabolism
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • CD3 Complex
  • I kappa B beta protein
  • I-kappa B Proteins
  • NF-kappa B
  • Ionomycin
  • Protein Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Tetradecanoylphorbol Acetate