On the role of melanoma-specific CD8+ T-cell immunity in disease progression of advanced-stage melanoma patients.
Cytotoxic T-cell immunity directed against melanosomal differentiation antigens is arguably the best-studied and most prevalent form of tumor-specific T-cell immunity in humans. Despite this, the role of T-cell responses directed against melanosomal antigens in disease progression has not been elucidated. To address this issue, we have related the presence of circulating melanoma-specific T cells with disease progression and survival in a large cohort of patients with advanced-stage melanoma who had not received prior treatment. In 42 (68%) of 62 patients, melanoma-specific T cells were detected, sometimes in surprisingly large numbers. Disease progression during treatment was more frequent in patients with circulating melanoma-specific T cells, and mean survival of patients with circulating melanoma-specific T cells was equal to the survival of patients without melanoma-specific T cells. These data suggest that the induction of melanosomal differentiation antigen-specific T-cell reactivity in advanced stage melanoma is a late event most likely due to antigen load and spreading and is not accompanied by a clinically significant antitumor effect. These melanoma-specific T cells may be functionally distinct from T cells raised during spontaneous regression or up vaccination.
Division of Immunology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
Monique
M
van Oijen
Adriaan
A
Bins
Sjoerd
S
Elias
Johan
J
Sein
Pauline
P
Weder
Gijsbert
G
de Gast
Henk
H
Mallo
Maarten
M
Gallee
Harm
H
Van Tinteren
Ton
T
Schumacher
John
J
Haanen
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D015234:HLA-A Antigens / Q000032:analysis; D015789:HLA-A2 Antigen; D006801:Humans; D007150:Immunohistochemistry; D058965:MART-1 Antigen; D008545:Melanoma / Q000097:blood / Q000276:immunology / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000276:immunology; D016019:Survival Analysis; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D016827:CD8 Antigens; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase