Alterations in T cell receptor and signal transduction molecules in melanoma patients.
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.
Zea
A H
AH
Immunotherapy Laboratory, Applications International Corporation, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201, USA.
Curti
B D
BD
Longo
D L
DL
Alvord
W G
WG
Strobl
S L
SL
Mizoguchi
H
H
Creekmore
S P
SP
O'Shea
J J
JJ
Powers
G C
GC
Urba
W J
WJ
D000328:Adult; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000401:mortality / Q000556:secondary; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism
D000951:Antigens, Neoplasm; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C054979:antigen T cell receptor, zeta chain; C494957:FYN protein, human; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn