Hodgkin’s lymphoma RNA-transfected dendritic cells induce cancer/testis antigen-specific immune responses

Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06097, Halle, Germany.
Cancer Immunology and Immunotherapy (Impact Factor: 3.94). 03/2012; 61(10):1769-79. DOI: 10.1007/s00262-012-1239-z
Source: PubMed


Cytotoxic T lymphocytes (CTL) can kill Hodgkin's lymphoma (HL) cells, and CTL have been used for the treatment of Epstein-Barr virus (EBV)-positive HL. For patients with EBV-negative HL, this strategy cannot be employed and alternative target structures have to be defined. In order to establish a system for the stimulation of HL-reactive T cells, we used dendritic cells (DC) as antigen-presenting cells for autologous T cells and transfected these DC with RNA from established HL cell lines. After stimulation of peripheral blood mononuclear cells (PBMC) with RNA-transfected DC, we analyzed the reactivity of primed PBMC by interferon gamma enzyme-linked immunospot. Our results suggest the presence of antigens with expression in HL cell lines and recognition of these antigens in combination with DC-derived human leukocyte antigen molecules. By the analysis of Gene Expression Omnibus microarray data sets from HL cell lines and primary HL samples in comparison with testis and other normal tissues, we identified HL-associated cancer testis antigens (CTA) including the preferentially expressed antigen in melanoma (PRAME). After stimulation of PBMC with RNA-transfected DC, we detected PRAME-reactive T cells. PRAME and other HL-associated CTA might be targets for HL-specific immune therapy or for the monitoring of HL-directed immune responses.

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Available from: Alexander Emmer, Aug 25, 2014
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    • "HL high sensitivity to radio- and chemotherapy is known for a long time and has led to the development of highly effective treatment regimens (reviewed in (60)). H2A.Bbd is specifically overexpressed in HL cell lines and in HL cells in vivo (17) and might be involved in the high success of radio- and chemotherapy for treatment of these patients. "
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    • "Most of our knowledge about PRAME comes from the analysis of solid tumors or leukemia cells. All HL cell lines tested have higher expression of PRAME in comparison to normal blood cells [19]. HL cells with relatively low expression of PRAME (cell line L-540) show increased expression of PRAME after treatment with the de-methylating agent 5′-azacytidine [19]. "
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