Bacteria in Cancer Therapy: Renaissance of an Old Concept

Figure 1

Biological events of the intrinsic tumor therapeutic effect of Salmonella. Steps  (1)–(4) depict major biological events associated with an antitumor effect induced by Salmonella infection. (1) Tumor invasion. (2) Colonization. (3) Infection control. (4) Antitumor response and tumor regression. (1) Presence of bacteria in the blood stream (bacteremia) induces a cytokine storm, which is dominated by vasoactive cytokines that facilitate passive deposition of bacteria in the tumor during the induced hemorrhage. (2) Invading bacteria accumulate, localize to a preferable growth environment (low p0₂, immune privileged site), and proliferate to saturation. (3) Colonization brings about change to the tumor microenvironment, including attraction and polarization of innate effector cells and cytokines in favor of antibacterial control and tumor immune surveillance. (4) Tumor regression occurs in response to multimodal therapeutic effects, including an adjuvant effect on preestablished tumor immune surveillance, polarization of innate effectors’ phenotype, direct cytotoxicity, and passive effects.