Granulocyte/macrophage-colony-stimulating factor augments lymphokine-activated killer activity from lymphocytes via macrophages in lung cancer patients.
BACKGROUND
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.


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.


CONCLUSIONS
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.
Takahashi
K
K
The Second Department of Surgery, School of Medicine, The University of Tokushima, Japan. tkeiji@clin.med.tokushima-u.ac.jp
Saito
S
S
Kamamura
Y
Y
Katakawa
M
M
Monden
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D008175:Lung Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics; D009928:Organ Specificity; D010994:Pleura / Q000276:immunology; D021122:Protein Subunits; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007376:Interleukin-2; D009363:Neoplasm Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor