Methylation-regulated expression of cancer testis antigens in primary effusion lymphoma: Immunotherapeutic implications

Authors

  • Luana Calabrò,

    1. Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
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  • Ester Fonsatti,

    1. Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
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  • Maresa Altomonte,

    1. Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
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  • Laura Pezzani,

    1. Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
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  • Francesca Colizzi,

    1. Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
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  • Paola Nanni,

    1. Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
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  • Valter Gattei,

    1. Clinical and Experimental Hematology Research Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
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  • Luca Sigalotti,

    1. Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
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  • Michele Maio

    Corresponding author
    1. Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy
    2. Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Siena, Italy
    • Division of Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Strada delle Scotte 14, 53100 Siena, Italy.
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  • L. Calabrò and E. Fonsatti contributed equally to this work.

Abstract

Primary effusion lymphoma (PEL) is a large B-cell neoplasm with an unfavorable prognosis and limited therapeutic options. In this study, cancer testis antigens (CTA) were investigated as potential immunotherapeutic targets in patients with PEL. Baseline expression of a panel of 11 CTA was highly heterogeneous among five PEL cell lines. In particular, the investigated CTA were not expressed in BC-2 and BC-3 cells, while BC-1, HBL-6, and BCBL-1 cells tested positive for 6, 8, and 9 CTA, respectively. The DNA hypomethylating agent 5-aza-2′-deoxycytdine (5-AZA-CdR) invariably induced or up-regulated the expression of all investigated CTA in all cell lines analyzed. The de novo expression of CTA was still detectable at mRNA and protein level at least 2 months after the end of 5-AZA-CdR treatment. These findings, and the concomitant up-regulation of HLA-class I antigens and ICAM-1 by 5-AZA-CdR, support its clinical use to set-up innovative chemo-immunotherapeutic approaches in PEL. © 2004 Wiley-Liss, Inc.

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