Monocytes mediate Salmonella Typhimurium-induced tumour growth inhibition

Abstract

The use of bacteria as an alternative cancer therapy has been re-investigated in recent years. A number of bacterial strains for this purpose have been generated, one of which is SL7207: an auxotrophic Salmonella enterica serovar Typhimurium aroA mutant with immune-stimulatory potential. Here we show that systemic administration of SL7207 induces melanoma tumour growth arrest in vivo, with greater survival of the SL7207-treated group compared to control PBS-treated mice. Administration of SL7207 is accompanied by a change in the immune phenotype of the tumour-infiltrating cells towards pro-inflammatory, with expression of the TH1 cytokines IFN-{gamma}, TNF-, and IL-12 significantly increased. Interestingly, Ly6C+MHCII+ monocytes were recruited to the tumours following SL7207 treatment and were pro-inflammatory. Accordingly, the abrogation of these infiltrating monocytes using clodronate liposomes prevented SL7207-induced tumour growth inhibition. These data demonstrate a previously unappreciated role for infiltrating inflammatory monocytes underlying bacterial-mediated tumour growth inhibition. This information highlights a novel role for monocytes in controlling tumour growth, contributing to our understanding of the immune responses required for successful immunotherapy of cancer.