Ex vivo characterization of tumor-derived melanoma antigen encoding gene-specific CD8 + cells in patients with hepatocellular carcinoma

Alessandro Zerbini, Massimo Pilli, Paolo Soliani, Stefanie Ziegler, Guido Pelosi, Alessandra Orlandini, Cristina Cavallo, Jacopo Uggeri, Renato Scandroglio, Pellegrino Crafa, Giulio C. Spagnoli, Carlo Ferrari, Gabriele Missale

Research output: Contribution to journalArticle

Abstract

Background/Aims: 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.

Original languageEnglish
Pages (from-to)102-109
Number of pages8
JournalJournal of Hepatology
Volume40
Issue number1
DOIs
Publication statusPublished - Jan 2004

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Melanoma-Specific Antigens
Hepatocellular Carcinoma
Immunotherapy
Genes
Neoplasms
HLA-A1 Antigen
T-Lymphocytes
Phenotype
HLA-A2 Antigen
Neoplasm Antigens
Epitopes
Observation
Antigens

Keywords

  • Hepatocellular carcinoma
  • Immunotherapy
  • MAGE-3
  • Melanoma antigen encoding gene-1
  • Tumor immunity

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Ex vivo characterization of tumor-derived melanoma antigen encoding gene-specific CD8 + cells in patients with hepatocellular carcinoma. / Zerbini, Alessandro; Pilli, Massimo; Soliani, Paolo; Ziegler, Stefanie; Pelosi, Guido; Orlandini, Alessandra; Cavallo, Cristina; Uggeri, Jacopo; Scandroglio, Renato; Crafa, Pellegrino; Spagnoli, Giulio C.; Ferrari, Carlo; Missale, Gabriele.

In: Journal of Hepatology, Vol. 40, No. 1, 01.2004, p. 102-109.

Research output: Contribution to journalArticle

Zerbini, A, Pilli, M, Soliani, P, Ziegler, S, Pelosi, G, Orlandini, A, Cavallo, C, Uggeri, J, Scandroglio, R, Crafa, P, Spagnoli, GC, Ferrari, C & Missale, G 2004, 'Ex vivo characterization of tumor-derived melanoma antigen encoding gene-specific CD8 + cells in patients with hepatocellular carcinoma', Journal of Hepatology, vol. 40, no. 1, pp. 102-109. https://doi.org/10.1016/S0168-8278(03)00484-7
Zerbini, Alessandro ; Pilli, Massimo ; Soliani, Paolo ; Ziegler, Stefanie ; Pelosi, Guido ; Orlandini, Alessandra ; Cavallo, Cristina ; Uggeri, Jacopo ; Scandroglio, Renato ; Crafa, Pellegrino ; Spagnoli, Giulio C. ; Ferrari, Carlo ; Missale, Gabriele. / Ex vivo characterization of tumor-derived melanoma antigen encoding gene-specific CD8 + cells in patients with hepatocellular carcinoma. In: Journal of Hepatology. 2004 ; Vol. 40, No. 1. pp. 102-109.
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AU - Pelosi, Guido

AU - Orlandini, Alessandra

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AU - Uggeri, Jacopo

AU - Scandroglio, Renato

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AB - Background/Aims: 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.

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