Johnson, Síle A.;
Ormsby, Michael J.;
Wessel, Hannah M.;
Hulme, Heather E.;
Bravo‐Blas, Alberto;
McIntosh, Anne;
Mason, Susan;
Coffelt, Seth B.;
Tait, Stephen W.G.;
Mowat, Allan McI.;
Milling, Simon W.F.;
Blyth, Karen;
Wall, Daniel M.
Monocytes mediate Salmonella Typhimurium‐induced tumor growth inhibition in a mouse melanoma model
Description:
<jats:title>Abstract</jats:title><jats:p>The use of bacteria as an alternative cancer therapy has been reinvestigated in recent years. SL7207: an auxotrophic <jats:italic>Salmonella enterica</jats:italic> serovar Typhimurium <jats:italic>aroA</jats:italic> 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<jats:sub>H</jats:sub>1 cytokines IFN‐γ, TNF‐α, and IL‐12 significantly increased. Interestingly, Ly6C<jats:sup>+</jats:sup>MHCII<jats:sup>+</jats:sup> 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.</jats:p>