SALL4 oncogene is an immunogenic antigen presented in various HLA-DR contexts.
Fiche publication
Date publication
janvier 2018
Journal
Oncoimmunology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier, Pr BORG Christophe, Dr FERRAND Christophe, Dr GODET Yann, Dr LAROSA Fabrice, Dr KIM Stephano, Dr GALAINE Jeanne, Dr KROEMER Marie
Tous les auteurs :
Kroemer M, Spehner L, Mercier-Letondal P, Boullerot L, Kim S, Jary M, Galaine J, Picard E, Ferrand C, Nguyen T, Larosa F, Adotévi O, Godet Y, Borg C
Lien Pubmed
Résumé
: To investigate the immunoprevalence of SALL4-derived peptides in healthy volunteers and cancer patients. : A multistep approach including prediction algorithms was used to design SALL4-derived peptides theoretically able to bind on common HLA-DR and HLA-A/B molecules. The presence of T-cell responses after a long term T-cell assay (28 days) against SALL4 was monitored in 14 healthy donors and the presence of T-cell responses after a short term T-cell assay (10 days) was monitored in 67 cancer patients using IFN-γ ELISPOT assay. A T-cell clone specific for the immunoprevalent A18 K-derived peptide was isolated, characterized and used as a tool to characterize the natural processing of A18 K. : A SALL4 specific T-cell repertoire was present in healthy donors (8/14) and cancer patients (29/67) after short term T-cell assay. We further identified two immunoprevalant SALL4-derived peptides, R18 A and A18 K, which bind MHC-class II. In parallel, an A18 K specific Th1 clone recognized monocyte derived Dendritic Cell (moDC) loaded with SALL4 containing cell lysate. The level of IFN-γ secreted by specific T-cell clone was greater in presence of moDC loaded with SALL4 containing cell lysate (49.23 ± 14.02%) than with moDC alone (18.03 ± 3.072%) (p = 0.0477) : These results show for the first time immunogenicity of SALL4 oncogenic protein-derived peptides, especially A18 K and R18 A peptides and make them potential targets for personalized medicine. Thus, SALL4 possess major characteristics of a tumor antigen.
Mots clés
Cancer, Immunotherapy, SALL4, T Lymphocytes, Tumor antigen
Référence
Oncoimmunology. 2018 ;7(4):e1412030