Macrophages in tumor-draining lymph node with different characteristics induce T-cell apoptosis in patients with advanced stage-gastric cancer.
A host's immune-defense system is suppressive by many factors in patients with cancer. We have previously shown one possible mechanism behind the T-cell dysfunction, whereby H(2)O(2) secreted from macrophages in tumor-draining lymph node (MTDL) induced T-cell dysfunction with down-regulation of TCR zeta molecules. In the present study, we analyzed how MTDL affect T cells, with a particular focus on T-cell apoptosis, by co-culturing MTDL with autologous peripheral blood T cells in gastric cancer. Moreover, we characterized the MTDL according to surface marker, oxygen-burst capacity and intracellular cytokine status. T-cell apoptosis was significantly induced in comparison to T-cell alone control in patients with advanced disease, concomitant to the elevated caspase activity and following impaired T-cell function. In patients with early disease, no significant difference was seen in the proportions of T cells that underwent apoptosis between T cells plus MTDL and T cells alone. Moreover, the addition of a selective scavenger of H(2)O(2), catalase inhibited the apoptosis of T cells co-cultured with MTDL in patients with advanced disease. In the characterization of MTDL, the production of H(2)O(2) in MTDL from advanced disease was significantly higher than that in early disease. The amounts of intracellular IL-10 and IL-12 in MTDL in advanced disease were significantly higher than those in early disease. These results indicated that MTDL induced apoptosis of autologous T cells and this T-cell dysfunction was mediated by H(2)O(2) derived from MTDL. Furthermore, the characteristics of MTDL including the capacity of oxygen-burst and intracellular cytokine production were different depending on the disease progression.
Takahashi
Akihiro
A
First Department of Surgery, Yamanashi Medical University, Tamaho, Yamanashi, Japan.
Kono
Koji
K
Ichihara
Fumiko
F
Sugai
Hidemitsu
H
Amemiya
Hideki
H
Iizuka
Hidehiko
H
Fujii
Hideki
H
Matsumoto
Yoshiro
Y
D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D018920:Coculture Techniques; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology*; D008264:Macrophages / Q000502:physiology*; D008565:Membrane Proteins / Q000032:analysis; D009367:Neoplasm Staging; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D016897:Respiratory Burst; D013274:Stomach Neoplasms / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000502:physiology*
D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases