Characteristic alteration of monocytes with increased intracellular IL-10 and IL-12 in patients with advanced-stage gastric cancer.
BACKGROUND
It was previously reported that monocytes/macrophages play an important role in mediating T cell dysfunction in tumor-bearing hosts, in which monocytes/macrophages were found to induce the loss of T cell functions concomitantly with induction of defects in T cell signaling molecules. These observations encouraged us to investigate monocytes status in cancer-bearing hosts.


METHODS
We characterized peripheral blood monocytes in gastric cancer patients with advanced disease (n = 14), in those with early disease (n = 17), and in healthy individuals (n = 14), based on surface marker, oxygen-burst capacity, and intracellular cytokine status (IL-10 and IL-12).


RESULTS
Intracellular IL-10 and IL-12 status on monocytes in advanced disease was significantly increased in comparison with those in early disease or healthy individuals, while there were no differences in the surface marker or oxygen-burst capacity of monocytes. To clarify which mediators induced the characteristic differences of monocytes in cancer-bearing hosts, healthy donor-derived monocytes were coincubated with the patient's plasma. The plasma from the patients with advanced disease could induce healthy monocytes to increased intracellular IL-10 and IL-12 status. The phenomenon was significantly inhibited with neutralizing mAbs specific for VEGF. Furthermore, the contents of VEGF in the patient's plasma correlated with their capacity to induce healthy monocytes to increased intracellular IL-10. In addition, the treatment of healthy monocytes with exogenous VEGF resulted in increased intracellular IL-10.


CONCLUSIONS
Monocytes in gastric cancer patients with advanced disease showed different characteristics in comparison with those with early disease or healthy individuals, which might be potentially induced by circulating VEGF in the patients.
Sugai
Hidemitsu
H
First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Kono
Koji
K
Takahashi
Akihiro
A
Ichihara
Fumiko
F
Kawaida
Hiromitsu
H
Fujii
Hideki
H
Matsumoto
Yoshiro
Y
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001782:Blood Donors; D001790:Blood Physiological Phenomena; D016022:Case-Control Studies; D002452:Cell Count; D004731:Endotoxins / Q000097:blood; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism* / Q000473:pathology*; D013274:Stomach Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D018664:Interleukin-12; D006861:Hydrogen Peroxide