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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 10/2004

01-10-2004 | Review

Down-regulation of ζ-chain expression in T cells: a biomarker of prognosis in cancer?

Author: Theresa L. Whiteside

Published in: Cancer Immunology, Immunotherapy | Issue 10/2004

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Abstract

The ζ chain is a 16-kDa molecule associated with the T-cell receptor (TCR)-CD3 complex in T lymphocytes and FcγRIII in CD3−CD56+CD16+ natural killer (NK cells). The ζ chain functions as a transmembrane signaling molecule in lymphocytes. Expression of ζ was found to be decreased in CD4+ and CD8+ T lymphocytes isolated from the tumor site or from the peripheral circulation of patients with cancer. A quantitative flow cytometry–based assay for ζ-chain expression allows for reproducible serial evaluations of disease- or therapy-associated changes in expression of this signaling molecule in phenotypically defined subsets of immune cells. Semiquantitative evaluation of ζ expression in paraffin-embedded tissue specimens can link it to the conventional markers of prognosis or survival. Several distinct mechanisms may be responsible for decreased/absent ζ in T cells of patients with cancer. Monitoring for ζ expression is useful for assessing immune competence in these patients and for following changes in immune competence during anticancer therapies. Correlations made between clinical findings, pathologic results, and ζ expression in immune cells suggest that low/absent ζ is predictive of poor prognosis and survival in patients with cancer. Thus, ζ is emerging as a clinically relevant signaling molecule, which also seems to predict a favorable response to biologic therapies and could be helpful in a selection of patients for immunotherapy trials. Validation studies have yet to be performed for this putative immunologic biomarker. Its consistent use for monitoring under standardized conditions of cancer patients treated with biotherapies may help in confirming a role for ζ as a correlate of prognosis or survival.
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Metadata
Title
Down-regulation of ζ-chain expression in T cells: a biomarker of prognosis in cancer?
Author
Theresa L. Whiteside
Publication date
01-10-2004
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 10/2004
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-004-0521-0

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