Attenuated mutants of Typhimurium mediate melanoma regression via an immune response.

The lack of effective treatment options for an increasing number of cancer cases highlights the need for new anticancer therapeutic strategies. Immunotherapy mediated by Typhimurium is a promising anticancer treatment. Candidate strains for anticancer therapy must be attenuated while retaining their antitumor activity. Here, we investigated the attenuation and antitumor efficacy of two Typhimurium mutants, Δ and Δ, in a murine melanoma model. Results showed high attenuation of Δ in the model, and invasion and survival in tumor cells. However, it showed weak antitumor effects and . Contrastingly, lower attenuation of the attenuated Δ strain resulted in regression of tumor mass in all mice, approximately 6 days after the first treatment. The therapeutic response induced by Δ was accompanied with macrophage accumulation of antitumor phenotype (M1) and significant increase in the mRNAs of proinflammatory mediators (TNF-α, IL-6, and iNOS) and an apoptosis inducer (Bax). Our findings indicate that the attenuated Δ exerts its antitumor activity by inducing macrophage infiltration or reprogramming the immunosuppressed tumor microenvironment to an activated state, suggesting that attenuated Typhimurium strains based on nucleoid-associated protein genes deletion could be immunotherapeutic against cancer.