Impaired IFN-γ production after stimulation with bacterial components by natural killer cells from gastric cancer patients.
Gastric adenocarcinoma is a major health problem world-wide, as this is the second most common cause of cancer death in the world. It has been estimated that infection by Helicobacter pylori cause at least half of the gastric cancers. Previously, we have demonstrated that H. pylori antigens directly activate NK cells to secrete IFN-γ. There is also a marked synergistic effect in NK cells stimulated with bacterial lysate and low levels of IL-12, a cytokine which is produced by macrophages and dendritic cells in the H. pylori-infected stomach. The present study was designed to investigate whether NK cells from gastric cancer patients display an altered ability to respond to components from H. pylori and other bacteria. The results show that NK cells from peripheral blood of gastric cancer patients have a severely suppressed ability to produce IFN-γ after stimulation with H. pylori lysate and the synthetic bacterial lipoprotein FSL-1. Furthermore, the synergistic effect of IL-12 and lysate is absent in gastric cancer patients, unless the concentration of IL-12 is increased 10-fold. We also demonstrate that there is a similar lack of IFN-γ production from NK cells isolated from the gastric mucosa of cancer patients. In addition, we propose that the observed suppression is due to tumour-derived TGF-β and that increased expression of the transcription factor GATA-3 may be responsible for the TGF-β induced suppression.
Institute of Biomedicine, Department of Microbiology and Immunology, and Mucosal Immunobiology and Vaccine Institute for Strategic Research, University of Gothenburg, Box 435, 405 30 Gothenburg, Sweden. asa.lindgren@microbio.gu.se
Åsa
Å
Lindgren
Cheol-Heui
CH
Yun
Åsa
Å
Sjöling
Camilla
C
Berggren
Jia-Bin
JB
Sun
Erik
E
Jonsson
Jan
J
Holmgren
Ann-Mari
AM
Svennerholm
Samuel B
SB
Lundin
D000368:Aged; D000942:Antigens, Bacterial / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism; D005753:Gastric Mucosa / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016481:Helicobacter Infections / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000276:immunology; D020825:T-Box Domain Proteins / Q000378:metabolism; D000098815:T-bet Transcription Factor
D000942:Antigens, Bacterial; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma