TY - JOUR
T1 - Comparative analysis of the in vivo expression of tyrosinase, MART- 1/Melan-A, and gp 100 in metastatic melanoma lesions
T2 - Implications for immunotherapy
AU - Cormier, J. N.
AU - Abati, A.
AU - Fetsch, P.
AU - Hijazi, Y. M.
AU - Rosenberg, S. A.
AU - Marincola, F. M.
AU - Topalian, S. L.
PY - 1998/2/3
Y1 - 1998/2/3
N2 - A variety of human melanoma-associated antigens (MAA) have been identified that can be recognized by T lymphocytes in a major histocompatibility complex-restricted fashion. Among them, tyrosinase, MART- 1/Melan- A, and gp100 are derived from nonmutated melanocyte lineage-specific antigens (Ag). These Ag can be recognized by CD8+ and, in the case of tyrosinase, CD4+ T cells. The in situ expression of MAA may be a significant cofactor in determining the recognition of melanoma targets by Ag-specific T cells. In this study, we examined the patterns of expression of these MAA using immunohistochemical methods on 30 metastatic tumor deposits derived from 25 patients. MAA expression was heterogeneous among the 30 specimens and also within individual lesions. Of note, 23% of the samples examined failed to express the gp100 protein, and 17% of samples had no detectable expression of MART-1. In contrast, all lesions demonstrated some degree of tyrosinase expression even in cases where both gp100 and MART-I were not detectable. In addition, 60% of samples (18 of 30) showed strong positivity for tyrosinase (>75% of cells staining) compared with 40% for gp100 and 36% for MART-1. Currently, a number of experimental immunotherapies for melanoma are directed against the MAA tyrosinase, MART-1, and gp100. Although threshold levels of Ag required for T-cell recognition have not yet been defined, tumor- associated Ag expressed in high density, such as tyrosinase, may be better targets for future immunotherapy trials.
AB - A variety of human melanoma-associated antigens (MAA) have been identified that can be recognized by T lymphocytes in a major histocompatibility complex-restricted fashion. Among them, tyrosinase, MART- 1/Melan- A, and gp100 are derived from nonmutated melanocyte lineage-specific antigens (Ag). These Ag can be recognized by CD8+ and, in the case of tyrosinase, CD4+ T cells. The in situ expression of MAA may be a significant cofactor in determining the recognition of melanoma targets by Ag-specific T cells. In this study, we examined the patterns of expression of these MAA using immunohistochemical methods on 30 metastatic tumor deposits derived from 25 patients. MAA expression was heterogeneous among the 30 specimens and also within individual lesions. Of note, 23% of the samples examined failed to express the gp100 protein, and 17% of samples had no detectable expression of MART-1. In contrast, all lesions demonstrated some degree of tyrosinase expression even in cases where both gp100 and MART-I were not detectable. In addition, 60% of samples (18 of 30) showed strong positivity for tyrosinase (>75% of cells staining) compared with 40% for gp100 and 36% for MART-1. Currently, a number of experimental immunotherapies for melanoma are directed against the MAA tyrosinase, MART-1, and gp100. Although threshold levels of Ag required for T-cell recognition have not yet been defined, tumor- associated Ag expressed in high density, such as tyrosinase, may be better targets for future immunotherapy trials.
KW - Gp100
KW - Immunotherapy
KW - MART-1
KW - Melanoma
KW - Tyrosinase
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U2 - 10.1097/00002371-199801000-00003
DO - 10.1097/00002371-199801000-00003
M3 - Article
C2 - 9456433
AN - SCOPUS:0031963115
VL - 21
SP - 27
EP - 31
JO - Journal of Biological Response Modifiers
JF - Journal of Biological Response Modifiers
SN - 1524-9557
IS - 1
ER -