Role of autophagy in antigen presentation and its involvement on cancer immunotherapy

Abstract Autophagy is a catabolic process in which cytosolic constituents such as damaged proteins and organelles are degraded by lysosomal hydrolases and this pathway therefore recycles nutrients and provides energy to the cells. In this review, we will describe the involvement of autophagy in antigen presentation and its impact on cancer immunotherapy. In antigen presenting cells, the autophagy pathway generates peptides from endogenous antigen presented by the major histocompatibility class II (MHC-II) proteins to CD4+ T cells. The contribution of CD4+ T cells in the immune response is crucial and central since they coordinate and increase the activity of every cell types involved in immunity and especially in the immunity against cancer. Autophagy is also important in antigen donor cells like for instance tumor cells. Indeed, when captured by antigen presenting cells, these exogenous antigens will be more efficiently presented on MHC-I by the mechanism of cross-presentation for a stronger priming of CD8+ T cells and a better cytotoxic activity. Finally, the involvement of autophagy in antigen presentation led to consider the modulation of autophagy as a mean to improve immunotherapy through three promising axes. Firstly, the release of autophagosomes by tumor cells treated with proteasome and autophagosome-lysosome fusion inhibitors or autophagic inducer is a source of tumor antigens for therapeutic vaccination. Secondly, fusion proteins between ATG8 family proteins or cargo adaptors and tumor antigens will specifically address the tumor antigens into autophagosomes in order to facilitate their MHC-II presentation and efficiently prime CD4+ T cells. Finally, the use of radiotherapy can increase autophagy in tumor cells, enhances MHC-I expression level at the surface of tumor cells making them better target for CD8+ T cell cytotoxicity.