Signaling defects in T lymphocytes of patients with malignancy |
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Authors: | Theresa L Whiteside |
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Institution: | (1) Department of Pathology and Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA, US;(2) University of Pittsburgh Cancer Institute, 211 Lothrop Street, W1041 BST, Pittsburgh, PA 15213, USA e-mail: whitesidetl@msx.upmc.edu Tel.: +1-412-6240096; Fax: +1-412-6240264, US |
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Abstract: | In patients with cancer, alterations in the expression of T-cell receptor-associated molecules in tumor-infiltrating lymphocytes
(TIL) as well as in circulating lymphocytes have been reported. By quantitative flow cytometry analysis, decreased or absent
expression of the ζ chain in CD4+ or CD8+ T cells as well as in natural killer (NK) cells was demonstrated in patients with malignancies. Changes in the expression
of ζ are biologically significant, because the absence or low expression of this signaling molecule in TIL of patients with
stage III or IV head and neck cancer predicts a significantly shorter 5-year survival than that of patients with normal ζ
expression in TIL. Preliminary evidence indicates that expression of ζ in TIL may not only influence survival but also predicts
a favorable response to biologic therapies. Patients with cancer also show significantly greater spontaneous ex vivo apoptosis
in peripheral blood mononuclear cells (PBMC) compared to normal controls, as measured by a terminal deoxynucleotide transferase-mediated
dUTP nick end labeling (TUNEL) assay. While no correlation could be established between the proportions of cells with low
ζ chain expression and those that spontaneously apoptose ex vivo, the ζ chain has been shown to be cleaved by caspases in
T cells coincubated with tumor cells or with T cells exposed to CH-11 antibody, which induces apoptosis upon crosslinking
Fas on the cell surface. The results suggest that low/absent ζ chain expression and lymphocyte apoptosis may be manifestations
of negative effects of the tumor on the host immune system.
Received: 20 March 1999 / Accepted: 3 May 1999 |
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Keywords: | Tumor-infiltrating lymphocytes ζ chain expression Malignancy Lymphocyte apoptosis |
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