Last
Updated: 2003-05-23 14:13:36 -0400 (Reuters Health)
NEW YORK (Reuters Health) - In patients with tumors, down-regulation of
T cell signaling is related to T cell apoptosis. Now, a team of Japanese
researchers has found new clues to the relationship between macrophages
in tumor-draining lymph nodes and T cell apoptosis in cancer patients.
In the May issue of the International Journal of Cancer, Dr. Akihiro
Takahashi and colleagues at the Yamanashi Medical University describe
experiments in which they co-cultured macrophages in tumor-draining
lymph nodes with autologous peripheral blood T cells from patients with
various stages of gastric cancer.
In samples from patients with very early disease, rates of apoptosis
were similar in the co-cultured T cells and in control T cells. In
samples from patients with advanced disease, however, a significantly
greater proportion of co-cultured T cells underwent apoptosis compared
with control T cells. Apoptosis in the co-cultured T cells correlated
with elevated caspase activity and followed impaired T cell function,
according to the report.
The authors note that "addition of a selective scavenger of
[hydrogen peroxide] inhibited the apoptosis of T cells co-cultured with
macrophages in tumor-draining lymph nodes in patients with advanced
disease."
In addition, they note, the production of hydrogen peroxide was
"significantly higher" in macrophages in tumor-draining lymph
nodes from patients with advanced disease compared with macrophages from
those with early disease. Furthermore, levels of interleukin-10 and
interleukin-12 were higher in the macrophages in tumor-draining lymph
nodes from patients with advanced disease.
"This is the first study that demonstrates that macrophages in
tumor-draining lymph nodes induce apoptosis of autologous T cells,
concomitant to...elevated caspase activity and following impaired T-cell
function," the investigators state.
In the future, they add, "normalization of T-cell function by
antioxidant therapy or manipulation of tumor-associated macrophages
should precede more specific immune interventions [such as] vaccination
with defined tumor antigens and cytokine-induced activation of T
cells."
Int J Cancer 2003; 104:393-399.
