Necroptotic extracellular vesicles - present and future

Abstract

Necroptosis is a receptor-interacting protein kinase 3 (RIPK3)-/mixed lineage kinase domain-like(MLKL)-dependent and caspase-independent form of cell death that promotes inflammation. We, and others, have recently shown that necroptotic cells release extracellular vesicles (EVs). This finding has highlighted that the impact of necroptosis extends well beyond its cell death function. In this review, we summarize the general characteristics, biogenesis, and function of EVs, as well as their role in cancer. In addition, we outline our current knowledge regarding necroptotic EVs, including their recently discovered and analyzed proteome. We examine the accumulating evidence for a role for necroptosis in anti-tumor immunity. Finally, we suggest that necroptotic EVs play an important role in the necroptosis-induced immune response and may, therefore, be exploited in cancer immunotherapy applications.

Keywords: Cancer; Extracellular vesicles; Immunotherapy; MLKL; Necroptosis; RIPK1; RIPK3.