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Macrophages in tumor‐draining lymph node with different characteristics induce T‐cell apoptosis in patients with advanced stage‐gastric cancer
Author(s) -
Takahashi Akihiro,
Kono Koji,
Ichihara Fumiko,
Sugai Hidemitsu,
Amemiya Hideki,
Iizuka Hidehiko,
Fujii Hideki,
Matsumoto Yoshiro
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10973
Subject(s) - apoptosis , t cell , immune system , lymph node , cancer , intracellular , immunology , cytokine , cancer cell , medicine , biology , cancer research , cell , microbiology and biotechnology , biochemistry
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 ζ 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. © 2003 Wiley‐Liss, Inc.