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

• Published in: Cancer research (Chicago, Ill.) Ill.), 2003-02, Vol.63 (3), p.642-646
• Main Authors: BATRA, Raj K, YING LIN, SHARMA, Sherven, DOHADWALA, Mariam, JIE LUO, POLD, Mehis, DUBINETT, Steven M
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - enzymology; Adenocarcinoma - immunology; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Apoptosis - immunology; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - enzymology; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; CD3 Complex - immunology; Host-tumor relations. Immunology. Biological markers; 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; Medical sciences; 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; Tumors
• ISSN: 0008-5472; 1538-7445

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.