Ex vivo characterization of tumor-derived melanoma antigen encoding gene-specific CD8+cells in patients with hepatocellular carcinoma.
OBJECTIVE
Members of the melanoma antigen encoding gene family are expressed in tumors of different histological types but not in normal tissue. For this reason, they are attractive targets for cancer immunotherapy.


METHODS
In the present study, we analyzed the expression of MAGE-1 and -3 genes in the hepatocellular carcinoma (HCC) tissue as well as frequency, phenotype and function of circulating and tumor infiltrating CD8+ cells specific for HLA-A1 and -A2 restricted epitopes of MAGE-1 and -3.


RESULTS
Our study shows for the first time the presence of MAGE/tetramer+ CD8 cells in the tumor tissue of patients with HCC. These cells are able to recognize the MAGE-1 sequence 161-169 and the MAGE-3 sequence 271-279. In a patient with a particularly high frequency of MAGE-1 sequence 161-169-specific T cells, phenotypic and functional analysis was performed showing a phenotype of recently-primed CD8 cells (CD28+CD27+CD45RA-CCR7).


CONCLUSIONS
The observation of a spontaneous in vivo priming of a MAGE-specific T cell response in patients with HCC and the high frequency of MAGE antigens expression in this tumor, makes this antigen a potential candidate for a MAGE-specific immunotherapy in hepatocellular carcinoma.
Zerbini
Alessandro
A
Divisione Malattie Infettive ed Epatologia, Azienda Ospedaliera Universitaria di Parma, Via Gramsci 14, 43100 Parma, Italy.
Pilli
Massimo
M
Soliani
Paolo
P
Ziegler
Stefanie
S
Pelosi
Guido
G
Orlandini
Alessandra
A
Cavallo
Cristina
C
Uggeri
Jacopo
J
Scandroglio
Renato
R
Crafa
Pellegrino
P
Spagnoli
Giulio C
GC
Ferrari
Carlo
C
Missale
Gabriele
G
D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D058950:Melanoma-Specific Antigens; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D013194:Staining and Labeling
D000951:Antigens, Neoplasm; D016827:CD8 Antigens; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D012333:RNA, Messenger