Alterations in T cell receptor and signal transduction molecules in melanoma patients.

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.

• Authors: A H Zea, B D Curti, D L Longo, W G Alvord, S L Strobl, H Mizoguchi, S P Creekmore, J J O'Shea, G C Powers, W J Urba
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 1 Issue 11 Pg. 1327-35 (Nov 1995) ISSN: 1078-0432 [Print] United States
• PMID: 9815928 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Membrane Proteins
• Proto-Oncogene Proteins
• Receptors, Antigen, T-Cell
• Receptors, Antigen, T-Cell, alpha-beta
• Receptors, Antigen, T-Cell, gamma-delta
• antigen T cell receptor, zeta chain
• FYN protein, human
• Fyn protein, mouse
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
• Proto-Oncogene Proteins c-fyn

Topics

• Adult
• Animals
• Antigens, Neoplasm (metabolism)
• Female
• Humans
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck) (metabolism)
• Male
• Melanoma (immunology, mortality, secondary)
• Membrane Proteins (metabolism)
• Mice
• Middle Aged
• Prognosis
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-fyn
• Receptors, Antigen, T-Cell (metabolism)
• Receptors, Antigen, T-Cell, alpha-beta (metabolism)
• Receptors, Antigen, T-Cell, gamma-delta (metabolism)