Oncotarget

Research Papers:

IRES-dependent translation of the long non coding RNA meloe in melanoma cells produces the most immunogenic MELOE antigens

Maud Charpentier, Mikael Croyal, Delphine Carbonnelle, Agnès Fortun, Laetitia Florenceau, Catherine Rabu, Michel Krempf, Nathalie Labarrière and François Lang _

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Oncotarget. 2016; 7:59704-59713. https://doi.org/10.18632/oncotarget.10923

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Abstract

Maud Charpentier1, Mikael Croyal2,3, Delphine Carbonnelle1, Agnès Fortun1, Laetitia Florenceau1,4, Catherine Rabu1, Michel Krempf2,3,4, Nathalie Labarrière1,4, François Lang1

1CRCNA, INSERM, CNRS, Université d’Angers, Université de Nantes, Nantes, France

2UMR INRA 1280, CHU, Nantes, France

3West Human Nutrition Research Center, CHU, Nantes, France

4CHU, Nantes, France

Correspondence to:

François Lang, email: francois.lang@univ-nantes.fr

Keywords: melanoma, IRES, long non coding RNA, tumor antigens, immunotherapy

Received: June 07, 2016     Accepted: July 20, 2016     Published: July 29, 2016

ABSTRACT

MELOE-1 and MELOE-2, two highly specific melanoma antigens involved in T cell immunosurveillance are produced by IRES-dependent translation of the long « non coding » and polycistronic RNA, meloe. In the present study, we document the expression of an additional ORF, MELOE-3, located in the 5′ region of meloe. Data from in vitro translation experiments and transfection of melanoma cells with bicistronic vectors documented that MELOE-3 is exclusively translated by the classical cap-dependent pathway. Using a sensitive tandem mass spectrometry technique, we detected the presence of MELOE-3 in total lysates of both melanoma cells and normal melanocytes. This contrasts with our previous observation of the melanoma-restricted expression of MELOE-1 and MELOE-2. Furthermore, in vitro stimulation of PBMC from 6 healthy donors with overlapping peptides from MELOE-1 or MELOE-3 revealed a very scarce MELOE-3 specific T cell repertoire as compared to the abundant repertoire observed against MELOE-1. The poor immunogenicity of MELOE-3 and its expression in melanocytes is consistent with an immune tolerance towards a physiologically expressed protein. In contrast, melanoma-restricted expression of IRES-dependent MELOE-1 may explain its high immunogenicity. In conclusion, within the MELOE family, IRES-dependent antigens represent the best T cell targets for immunotherapy of melanoma.


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