越来越多的癌症病例缺乏有效的治疗方案，凸显了对新的抗癌治疗策略的需求。由肠鼠伤寒沙门氏菌介导的免疫疗法是一种有前途的抗癌治疗方法。用于抗癌治疗的候选菌株必须被减毒，同时保留其抗肿瘤活性。在这里，我们研究了两种鼠伤寒沙门氏菌突变体 ΔtolRA 和 ΔihfABpmi 在小鼠黑色素瘤模型中的减毒和抗肿瘤功效。结果显示，大蜡螟模型中 ΔtolRA 高度减弱，肿瘤细胞侵袭和存活。然而，它在体外和体内表现出较弱的抗肿瘤作用。相比之下，首次治疗后约 6 天，减毒 ΔihfABpmi 菌株的减毒效果较低，导致所有小鼠的肿瘤质量消退。 ΔihfABpmi 诱导的治疗反应伴随着巨噬细胞抗肿瘤表型 (M1) 的积累以及促炎介质 (TNF-α、IL-6 和 iNOS) 和凋亡诱导剂 (Bax) mRNA 的显着增加。我们的研究结果表明，减毒的 ΔihfABpmi 通过诱导巨噬细胞浸润或将免疫抑制的肿瘤微环境重新编程至激活状态来发挥其抗肿瘤活性，这表明基于核样蛋白相关蛋白基因缺失的减毒鼠伤寒沙门氏菌菌株可以对癌症进行免疫治疗。 2024 佩雷斯·豪尔赫、贡蒂霍、席尔瓦、戈斯、海梅斯-弗洛雷斯、科瑟、罗查、乔治和布罗基。

The lack of effective treatment options for an increasing number of cancer cases highlights the need for new anticancer therapeutic strategies. Immunotherapy mediated by Salmonella enterica 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 S. enterica Typhimurium mutants, ΔtolRA and ΔihfABpmi, in a murine melanoma model. Results showed high attenuation of ΔtolRA in the Galleria mellonella model, and invasion and survival in tumor cells. However, it showed weak antitumor effects in vitro and in vivo. Contrastingly, lower attenuation of the attenuated ΔihfABpmi strain resulted in regression of tumor mass in all mice, approximately 6 days after the first treatment. The therapeutic response induced by ΔihfABpmi 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 ΔihfABpmi exerts its antitumor activity by inducing macrophage infiltration or reprogramming the immunosuppressed tumor microenvironment to an activated state, suggesting that attenuated S. enterica Typhimurium strains based on nucleoid-associated protein genes deletion could be immunotherapeutic against cancer.Copyright © 2024 Pérez Jorge, Gontijo, Silva, Goes, Jaimes-Florez, Coser, Rocha, Giorgio and Brocchi.