Clinical significance of MART-1 and HLA-A2 expression and CD8+ T cell infiltration in melanocytic lesions in HLA-A2 phenotype patients.
MART-1 is a good candidate antigen for immunotherapy against HLA-A2 patients with melanoma, since it is a highly immunogenic antigen recognized by HLA-A2 and HLA-B45 restricted CD8+ cytotoxic T cells and expressed in the majority of melanoma lesions. In the present study the expression of MART-1 and HLA-A2 on melanocytic cells and CD8+ T cell infiltration was immunohistochemically analyzed. MART-1 was expressed in most melanocytic lesions, while HLA-A2 was down-regulated with melanoma disease progression. Furthermore, concomitant down-regulation of MART-1 and HLA-A2 in melanoma cells was correlated with poor prognosis. These findings suggest both MART-1 and HLA-A2 expression in melanoma lesions should be analyzed for selection of patients eligible for MART-1 based immunotherapy and monitoring for emergence of melanoma cells resistant to T cell therapy.
Kageshita
T
T
Department of Dermatology, Kumamoto University School of Medicine, 1-1 Honjo, 860-0811, Kumamoto, Japan. toshiro@kaiju.medic.kumamoto-u.ac.jp
Kawakami
Y
Y
Ono
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D002648:Child; D005260:Female; D015789:HLA-A2 Antigen / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D058965:MART-1 Antigen; D008297:Male; D008544:Melanocytes / Q000473:pathology*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D012871:Skin Diseases / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D013194:Staining and Labeling
D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins