DC-Derived Exosomes for Cancer Immunotherapy

Abstract

Simple SummaryDendritic cells (DCs)-based cancer vaccines have not succeeded in generating significant clinical responses despite their capacity to induce host anti-tumor CD8 T cell immunity, and one major hurdle is tumor-mediated immunosuppression. Exosomes are nano-sized inert membrane vesicles derived from the endocytic pathway that play a critical role in intercellular communication. DC-derived exosomes (DCexos) additionally carried MHC class I/II (MHCI/II) often complexed with antigens and co-stimulatory molecules, thus capable of priming antigen-specific CD4 and CD8 T cells. Indeed, vaccines with DCexos have been shown to exhibit better anti-tumor efficacy in eradicating tumors compared to DC vaccines in pre-clinical models. Coupled with their resistance to tumor immunosuppression, DCexo-based cancer vaccines have been heralded as the superior alternative cell-free therapeutic vaccines over DC vaccines, and have now been tested in multiple clinical trials. In this review, current studies of DCexo cancer vaccines as well as potential future directions will be discussed.As the initiators of adaptive immune responses, DCs play a central role in regulating the balance between CD8 T cell immunity versus tolerance to tumor antigens. Exploiting their function to potentiate host anti-tumor immunity, DC-based vaccines have been one of most promising and widely used cancer immunotherapies. However, DC-based cancer vaccines have not achieved the promised success in clinical trials, with one of the major obstacles being tumor-mediated immunosuppression. A recent discovery on the critical role of type 1 conventional DCs (cDC1s) play in cross-priming tumor-specific CD8 T cells and determining the anti-tumor efficacy of cancer immunotherapies, however, has highlighted the need to further develop and refine DC-based vaccines either as monotherapies or in combination with other therapies. DC-derived exosomes (DCexos) have been heralded as a promising alternative to DC-based vaccines, as DCexos are more resistance to tumor-mediated suppression and DCexo vaccines have exhibited better anti-tumor efficacy in pre-clinical animal models. However, DCexo vaccines have only achieved limited clinical efficacy and failed to induce tumor-specific T cell responses in clinical trials. The lack of clinical efficacy might be partly due to the fact that all current clinical trials used peptide-loaded DCexos from monocyte-derived DCs. In this review, we will focus on the perspective of expanding current DCexo research to move DCexo cancer vaccines forward clinically to realize their potential in cancer immunotherapy.