Engineering Salmonella as an immune-metabolic modulator of the tumor microenvironment

Engineering bacteria as cancer therapeutics is gaining mounting attention due to the remarkable success in recent preclinical studies against several solid tumor models. Among the bacteria used, Salmonella stands out due to its inherent tumor localization ability, potential to activate the immune system, and ability to cause tumor regression, while having an easily editable genetic system. Here, we gather information on the mechanisms that enable Salmonella to stimulate the immune system and exert antitumor effects. We also address the genetic manipulation approaches adopted to reduce virulence, enhance tumor colonization, and equip Salmonella with the ability to deliver immunotherapeutic payloads, along with recent advances made in tumor metabolome rewiring. Finally, we propose the challenges associated with bacteria-based cancer therapy.