Systemic immune responses to irradiated tumours via the transport of antigens to the tumour periphery by injected flagellate bacteria

Flagellated bacteria coated with antigen-adsorbing polymer nanoparticles and injected into tumours in mice after radiotherapy elicit systemic antitumour effects by transporting antigens to the tumour's periphery. 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.

Automated summary

Flagellated bacteria coated with antigen-adsorbing polymer nanoparticles and injected into tumours in mice after radiotherapy elicit systemic antitumour effects by transporting antigens to the tumour's periphery. This finding highlights the potential of leveraging bacteria to enhance dendritic cell activation and improve in situ cancer vaccination strategies.