Depressed tumor necrosis factor alpha and interleukin-12p40 production by peripheral blood mononuclear cells of gastric cancer patients: association with IL-1R-associated kinase-1 protein expression and disease stage.
Our study investigated the ability of peripheral blood mononuclear cells (PBMCs) isolated from patients with different clinical stages of gastric cancer to produce proinflammatory (tumor necrosis factor alpha [TNFalpha], interleukin 12p40 [IL-12p40] and interleukin 6 [IL-6]) and antiinflammatory (interleukin-10 [IL-10]) cytokines after stimulation with lipopolysaccharide (LPS) or tumor cells, and its correlation with IL-1R-associated kinase-1 (IRAK-1) protein expression. The data showed that TNF production by tumor cell-stimulated PBMCs obtained from patients with advanced gastric cancer was significantly depressed in comparison to the control group. The response to LPS was less affected. IL-12p40 production was depressed in all stages of disease, while the release of IL-10 and IL-6 remained unchanged. Depressed tumor cell-induced TNF and IL-12p40 production was associated with diminished IRAK-1 protein expression in PBMC. These findings may suggest that in advanced gastric cancer (at least in some cancer patients) diminished IRAK-1 protein expression may be a novel mechanism responsible for or facilitating downregulation of innate immune response to tumor cells.
Siedlar
Maciej
M
Department of Clinical Immunology, Polish-American Institute of Paediatrics, Jagiellonian University Medical College, Krakow, Poland.
Szaflarska
Anna
A
Szczepanik
Antoni
A
Ruggiero
Irena
I
Frankenberger
Marion
M
Szatanek
Rafał
R
Czupryna
Antoni
A
Popiela
Tadeusz
T
Zembala
Marek
M
D000230:Adenocarcinoma / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D013274:Stomach Neoplasms / Q000097:blood* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D021122:Protein Subunits; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases