Systemic immune responses to irradiated tumours via the transport of antigens to the tumour periphery by injected flagellate bacteria
Menée in vitro et à l'aide de modèles murins, cette étude met en évidence l'intérêt d'injecter dans la tumeur une souche génétiquement atténuée de salmonelles recouvertes de nanoparticules de polymère cationique adsorbant les antigènes pour augmenter la réponse immunitaire antitumorale induite par une radiothérapie
Because the tumour microenvironment is typically immunosuppressive, the release of tumour antigens mediated by radiotherapy or chemotherapy does not sufficiently activate immune responses. Here we show that, following radiotherapy, the intratumoural injection of a genetically attenuated strain of Salmonella coated with antigen-adsorbing cationic polymer nanoparticles caused the accumulation of tumour antigens at the tumour’s periphery. This enhanced the crosstalk between the antigens and dendritic cells, and resulted in large increases in activated ovalbumin-specific dendritic cells in vitro and in systemic antitumour effects, and extended survival in multiple tumour models in mice, including a model of metastasis and recurrence. The antitumour effects were abrogated by the antibody-mediated depletion of CD8+ T cells, indicating that systemic tumour regression was caused by adaptive immune responses. Leveraging flagellate bacteria to transport tumour antigens to the periphery of tumours to potentiate the activation of dendritic cells may open up new strategies for in situ cancer vaccination.