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Mechanisms involved in the down‐regulation of TCR ζ chain in tumor versus peripheral blood of oral cancer patients
Author(s) -
Kulkarni Dakshayini P.,
Wadia Persis P.,
Pradhan Trupti N.,
Pathak Alok Kumar,
Chiplunkar Shubhada V.
Publication year - 2009
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.24137
Subject(s) - t cell receptor , biology , cd3 , immune system , immunoglobulin light chain , lymphocyte , t cell , cancer research , immunology , microbiology and biotechnology , cd8 , antibody
Abstract Immune dysfunction is the hallmark of patients with oral cancer. Down‐regulation of T cell receptor (TCR) ζ chain expression was observed in T cells from patients with oral squamous cell carcinoma. In peripheral blood, the decrease in TCR ζ chain showed an inverse correlation with the tumor stage as demonstrated by western blotting, confocal microscopy and flow cytometry. The mechanism of TCR ζ chain degradation in the peripheral blood involves ubiquitination and subsequent targeting of TCR ζ for degradation in the lysosome. Decreased expression of PKC θ and the subsequent decrease of TCR ζ chain transcription factor Elf‐1 and its binding to DNA may contribute to the decreased/or absent TCR ζ chain transcripts in the tumor infiltrating lymphocytes. Oral cancer patients exhibiting TCR ζ chain defect also showed impaired lymphocyte proliferation, cytokine profile and intracellular calcium release upon stimulation with anti CD3 mAb. Our data shows that posttranslational degradation is primarily responsible for decreased TCR ζ chain expression in the peripheral blood, while a transcriptional defect is observed in the tumor compartment. The down‐regulation of TCR ζ chain culminates into impaired lymphocyte responses in these patients. © 2008 Wiley‐Liss, Inc.