Expression of melanoma-associated antigens in melanoma cell cultures.
The efficiency of melanoma immunotherapy appears to depend on both melanoma- and immune system-specific factors. Melanoma-specific factors include melanoma-associated antigen (MAA) expression as well as HLA class I molecule expression. We investigated the expression of five MAA - Melan-A/MART-1, tyrosinase, gp100, MAGE-1 and MAGE-3 - by means of FACS analysis in 50 melanoma cell cultures and compared them to the cultures of human foreskin-derived melanocytes and melanoma cell line UKRV-Mel2. Melan-A, tyrosinase and gp100 expression was frequently reduced in melanoma cell cultures, compared to that in foreskin melanocytes, whereas MAGE-1 and MAGE-3 expression showed variable degree of upregulation, compared to that in foreskin melanocytes. The expression of all tested MAA demonstrated high interindividual variability. We further show that cell cultures derived from the same tissue sample are oligoclonal in nature, by demonstrating the presence of up to three cell populations bearing distinct MAA profile. Analysing samples derived from the same patient but each at a different time point, we show that MAA expression profile changes over time either in positive (increase) or in negative (decrease) direction. Finally, we demonstrate that brain metastasis-derived cell cultures significantly overexpress Melan-A and MAGE-3, compared to primary tumours and other metastatic sites (P-value range: 0.05-0.001). Elucidation of the MAA expression patterns and the kinetics within the same patient as well as during the course of the disease may help improve current and develop new immunotherapeutic strategies.
Urosevic
Mirjana
M
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. mirjana.urosevic@usz.ch
Braun
Bettina
B
Willers
Jörg
J
Burg
Günter
G
Dummer
Reinhard
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007370:Interferon Type I / Q000627:therapeutic use; D007700:Kinetics; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000556:secondary / Q000628:therapy; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000276:immunology / Q000378:metabolism; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; D007370:Interferon Type I; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D011994:Recombinant Proteins; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase