The ATG8 Family Proteins GABARAP and GABARAPL1 Target Antigen to Dendritic Cells to Prime CD4 and CD8 T Cells.

Fiche publication

Date publication

septembre 2022

Journal

Cells

Auteurs

Membres identifiés du Cancéropôle Est :
Dr ADAMI Pascale , Pr ADOTEVI Olivier , Pr GUITTAUT Michaël , Pr DELAGE-MOURROUX Régis

Tous les auteurs :
Fonderflick L, Baudu T, Adotévi O, Guittaut M, Adami P, Delage-Mourroux R

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/36139357

Résumé

Vaccine therapy is a promising method of research to promote T cell immune response and to develop novel antitumor immunotherapy protocols. Accumulating evidence has shown that autophagy is involved in antigen processing and presentation to T cells. In this work, we investigated the potential role of GABARAP and GABARAPL1, two members of the autophagic ATG8 family proteins, as surrogate tumor antigen delivery vectors to prime antitumor T cells. We showed that bone marrow-derived dendritic cells, expressing the antigen OVALBUMIN (OVA) fused with GABARAP or GABARAPL1, were able to prime OVA-specific CD4 T cells in vitro. Interestingly, the fusion proteins were also degraded by the proteasome pathway and the resulting peptides were presented by the MHC class I system. We then asked if the aforementioned fusion proteins could improve tumor cell immunogenicity and T cell priming. The B16-F10 melanoma was chosen as the tumor cell line to express the fusion proteins. B16-F10 cells that expressed the OVA-ATG8 fused proteins stimulated OVA-specific CD8 T cells, but demonstrated no CD4 T cell response. In the future, these constructions may be used in vaccination trials as potential candidates to control tumor growth.