Mechanisms involved in the down‐regulation of TCR ζ chain in tumor versus peripheral blood of oral cancer patients

Medientyp: E-Artikel

Titel: Mechanisms involved in the down‐regulation of TCR ζ chain in tumor versus peripheral blood of oral cancer patients

Beteiligte: Kulkarni, Dakshayini P.; Wadia, Persis P.; Pradhan, Trupti N.; Pathak, Alok Kumar; Chiplunkar, Shubhada V.

Erschienen: Wiley, 2009

Sprache: Englisch

DOI: 10.1002/ijc.24137

ISSN: 0020-7136; 1097-0215

Schlagwörter: Cancer Research ; Oncology

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Beschreibung: AbstractImmune 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.

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