1. Monocytes mediate Salmonella Typhimurium-induced tumor growth inhibition in a mouse melanoma model.
- Author
-
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, and Wall DM
- Subjects
- Animals, Cytokines immunology, Female, Mice, Salmonella typhimurium genetics, Immunotherapy, Melanoma, Experimental immunology, Melanoma, Experimental therapy, Monocytes immunology, Salmonella typhimurium immunology, Th1 Cells immunology
- 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 T
H 1 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., (© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)- Published
- 2021
- Full Text
- View/download PDF