Salmonella-Induced Cell Death in Cancer Immunotherapy: What Lies Beneath?

Bacteria-based cancer immunotherapies are regaining attention due to recent advances in understanding the mechanisms underlying their efficacy, making them promising tools for cancer treatment. Among these, Salmonella stands out as one of the most extensively studied microorganisms in this field. Its ability to directly induce tumor cell death while stimulating the immune system offers unique therapeutic advantages, as cell death within an inflammatory environment may enhance the release of tumor antigens and promote effective antitumor immune responses. Although multiple studies have addressed Salmonella-induced cell death, the nomenclature and classification of death modalities are often inconsistent-either because earlier reports predate the formalization of certain death pathways, or due to overlapping criteria between different types of cell death. This review aims to comprehensively analyze the available evidence on Salmonella-induced apoptosis, pyroptosis and autophagy, as well as other less characterized death modalities. Given that most mechanistics evidence on Salmonella-induced cell death has been generated in myeloid cells, we primarily focus on the myeloid compartment while integrating available observations from tumor cells and other immune populations when relevant, organizing the existing data under current definitions and concepts, and highlighting the challenges of manipulating these pathways to optimize bacterial-based immunotherapies.