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Impaired IFN-gamma Production after Stimulation with Bacterial Components by Natural Killer Cells from Gastric Cancer Patients

Artikel i vetenskaplig tidskrift
Författare Åsa Lindgren
Cheol H Yun
Åsa Sjöling
Camilla Berggren
Jia-Bin Sun
E Jonsson
Jan Holmgren
Ann-Mari Svennerholm
Samuel B Lundin
Publicerad i Experimental Cell Research
Volym 317
Nummer/häfte 6
Sidor 849-858
ISSN 0014-4827
Publiceringsår 2011
Publicerad vid Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi
Sidor 849-858
Språk en
Länkar dx.doi.org/10.1016/j.yexcr.2011.01....
Ämnesord NK cell; Gastric cancer; TGF-beta; IFN-gamma; Human
Ämneskategorier Immunbiologi, Tumörimmunologi

Sammanfattning

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.

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Utskriftsdatum: 2020-04-09