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  • Title: Granulocyte/macrophage-colony-stimulating factor augments lymphokine-activated killer activity from lymphocytes via macrophages in lung cancer patients.
    Author: Takahashi K, Saito S, Kamamura Y, Katakawa M, Monden Y.
    Journal: Cancer Immunol Immunother; 2000 Dec; 49(10):537-43. PubMed ID: 11129324.
    Abstract:
    INTRODUCTION: Therapies with granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin(IL)-2 are designed to activate macrophages and lymphocytes. We investigated whether combined treatment with GM-CSF and IL-2 induced macrophage-mediated antitumor activity and/or T-cell-mediated antitumor activity in lung cancer patients. PATIENTS AND METHODS: Macrophages in the pleural cavity (PCM), lymphocytes in the pleural cavity (PLY), and peripheral blood lymphocytes (PBL) were separated from 48 patients with resectable lung cancer. Lymphokine-activated killer (LAK) activity was assayed by measuring 51Cr release. The proportion of PCM positive for the GM-CSF receptor (GM-CFSR) alpha chain was examined by flow-cytometric analysis and the expression of GM-CSFR alpha chain mRNA in PCM was examined by reverse transcription/polymerase chain reaction analysis. RESULTS: Treatment with GM-CSF developed no significant antitumor activity in PCM, PLY, or PBL. LAK activity was developed by PLY and PBL after incubation with IL-2. Stimulation with GM-CSF augmented LAK activities in PLY and PBL significantly, when these cells were cultured with autologous PCM (P < 0.05, P < 0.01). Moreover, GM-CSFR-alpha-chain-positive PCM had a higher potential to augmented LAK activities in PLY and PBL than had GM-CSFR-alpha-chain-negative PCM. CONCLUSION: These findings suggest that GM-CSF may stimulate GM-CSFR-alpha-chain-positive PCM and that these PCM may augment LAK activities developed by PLY and PBL. Combined treatment with GM-CSF and IL-2, therefore, may be a reasonable approach to treating lung cancer patients.
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