Monocytes mediate Salmonella Typhimurium-induced tumor growth inhibition in a mouse melanoma model

Citation

Johnson SA, Ormsby MJ, Wessel HM, Hulme HE, Bravo‐Blas A, McIntosh A, Mason S, Coffelt SB, Tait SWG, Mowat AM, Milling SWF, Blyth K & Wall DM (2021) Monocytes mediate Salmonella Typhimurium-induced tumor growth inhibition in a mouse melanoma model. European Journal of Immunology, 51 (12), pp. 3228-3238. https://doi.org/10.1002/eji.202048913

Abstract
The use of bacteria as an alternative cancer therapy has been reinvestigated in recent years. SL7207: an auxotrophic Salmonella enterica serovar Typhimurium aroA mutant with immune-stimulatory potential has proven a promising strain for this purpose. Here, we show that systemic administration of SL7207 induces melanoma tumor 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 tumor-infiltrating cells toward pro-inflammatory, with expression of the TH1 cytokines IFN-γ, TNF-α, and IL-12 significantly increased. Interestingly, Ly6C+MHCII+ monocytes were recruited to the tumors following SL7207 treatment and were pro-inflammatory. Accordingly, the abrogation of these infiltrating monocytes using clodronate liposomes prevented SL7207-induced tumor growth inhibition. These data demonstrate a previously unappreciated role for infiltrating inflammatory monocytes underlying bacterial-mediated tumor growth inhibition. This information highlights a possible novel role for monocytes in controlling tumor growth, contributing to our understanding of the immune responses required for successful immunotherapy of cancer.

Keywords
Bacterial cancer therapy; Immunotherapy; Monocytes; SL7207

Journal
European Journal of Immunology: Volume 51, Issue 12

• Published version