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In recent years, cancer immunotherapy has undergone great advances because of our understanding of the immune response and the mechanisms through which tumor cells evade it. A century after the first immunotherapy attempt based on bacterial products described by William Coley, the use of live attenuated bacterial vectors has become a promising alternative in the fight against cancer. This review describes the role of live attenuated Salmonella enterica as an oncolytic and immunotherapeutic agent, due to its high affinity for tumor tissue and its ability to activate innate and adaptive antitumor immune response. Furthermore, its potential use as delivery system of tumor antigens and immunomodulatory molecules that induce tumor regression is also reviewed.

Salmonella enterica is a facultative anaerobic bacteria, whose ability to colonize antigen-presenting cells (APCs) such as dendritic cells and macrophages, has allowed its successful use as an alive, attenuated bacterial vector for vaccination. Salmonella enterica elicits efficient cellular, humoral and mucosal immune responses, against heterologous antigens including viruses, parasites, other bacterial species and tumor-associated antigens, since it is capable of delivering these antigens to cells of the immune system. The extracellular expression of heterologous antigens on the surface of Salmonella enterica via its type I, III and V secretion systems, and their delivery into infected cells is essential for its stimulation of immune responses against these antigens. Moreover, Salmonella enterica is a promising therapeutic agent against cancer, as demonstrated by reports of pre-clinical and clinical studies indicating that, after systemic administration, Salmonella enterica preferentially localizes in solid tumors and metastases as compared to normal tissues. In this review, we focus on novel prophylactic and therapeutic anti-cancer approaches using Salmonella enterica as a delivery system of heterologous molecules with the aim of inhibiting tumor growth.