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  • Title: Alterations in T cell receptor and signal transduction molecules in melanoma patients.
    Author: Zea AH, Curti BD, Longo DL, Alvord WG, Strobl SL, Mizoguchi H, Creekmore SP, O'Shea JJ, Powers GC, Urba WJ.
    Journal: Clin Cancer Res; 1995 Nov; 1(11):1327-35. PubMed ID: 9815928.
    Abstract:
    We have recently described molecular changes in T cells from tumor-bearing patients that are associated with depressed immune function. The present work investigates changes in T-cell signal transduction proteins including the T-cell receptor-zeta (TCR-zeta) chain and receptor-associated tyrosine kinases in patients with metastatic malignant melanoma. A marked decrease in the expression of the TCR-zeta chain was observed in the peripheral blood T cells of 19 (43%) of 44 patients. Decreases in several tyrosine kinases were found in 12 (57%) of 21 patients tested. T cells from patients with diminished TCR-zeta chain expression also showed statistically significant differences in cytokine production pattern, with lower interleukin 2 and IFN-zeta production compared with normal subjects and melanoma patients with normal TCR-zeta chain status. The overall survival of melanoma patients with low TCR-zeta chain expression was significantly shorter than that of patients with normal TCR-zeta chain expression (P = 0.0013). TCR-zeta-deficient patients showed a trend toward having faster growing tumors. There was no correlation between the pretreatment TCR-zeta chain status and albumin or performance status. These findings suggest that alterations in T-cell function occur commonly in melanoma patients and may be independent predictors of clinical outcome.
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