Bacteria-derived nanovesicles enhance tumour vaccination by trained immunity

Trained immunity enhances the responsiveness of immune cells to subsequent infections or vaccinations. Here we demonstrate that pre-vaccination with bacteria-derived outer-membrane vesicles, which contain large amounts of pathogen-associated molecular patterns, can be used to potentiate, and enhance, tumour vaccination by trained immunity. Intraperitoneal administration of these outer-membrane vesicles to mice activates inflammasome signalling pathways and induces interleukin-1β secretion. The elevated interleukin-1β increases the generation of antigen-presenting cell progenitors. This results in increased immune response when tumour antigens are delivered, and increases tumour-antigen-specific T-cell activation. This trained immunity increased protection from tumour challenge in two distinct cancer models. The level of immune response in cancer vaccines can limit application. Here, an immune mobilization strategy, using bacteria-derived nanovesicles, enhances therapeutic outcomes of tumour vaccination by stimulating interleukin-1β secretion to elicit trained immunity with lineage shifts and epigenetic changes in myeloid progenitor pools.