Monocytes mediate Salmonella Typhimurium-induced tumour growth inhibition

Johnson, S.; Ormsby, M. J.; Wessel, H. M.; Hulme, H.; Bravo Blas, A.; McIntosh, A.; Mason, S.; Coffelt, S. B.; Tait, S. W.; Mowat, A. M.; Milling, S.; Blyth, K.; Wall, D. M.

doi:10.1101/2020.05.13.092858

bioRxiv · 10.1101/2020.05.13.092858

Monocytes mediate Salmonella Typhimurium-induced tumour growth inhibition

Johnson, S.·Ormsby, M. J.·Wessel, H. M.·Hulme, H.·Bravo Blas, A.·McIntosh, A.·Mason, S.·Coffelt, S. B.·Tait, S. W.·Mowat, A. M.·Milling, S.·Blyth, K.·Wall, D. M.

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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.

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Johnson, S., Ormsby, M. J., Wessel, H. M., Hulme, H., Bravo Blas, A., McIntosh, A., Mason, S., Coffelt, S. B., Tait, S. W., Mowat, A. M., Milling, S., Blyth, K., Wall, D. M.. 2020-05-15. Monocytes mediate Salmonella Typhimurium-induced tumour growth inhibition. https://doi.org/10.1101/2020.05.13.092858

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