减毒鼠伤寒沙门氏菌可减轻原位乳腺癌模型中的肿瘤负担。

Attenuated Salmonella enterica Typhimurium reduces tumor burden in an autochthonous breast cancer model.

作者信息

Drees Jeremy, Mertensotto Michael, Liu Garvey, Panyam Jayanth, Leonard Arnold, Augustin Lance, Schottel Janet, Saltzman Daniel

机构信息

Department of Surgery, University of Minnesota, Minneapolis, MN, U.S.A.

Department of Pharmaceutics, University of Minnesota, Minneapolis, MN, U.S.A.

出版信息

Anticancer Res. 2015 Feb;35(2):843-9.

PMID:25667465

Abstract

BACKGROUND/AIM: Cancer treatment with attenuated Salmonella enterica Typhimurium (S. Typhimurium) has gained momentum in recent years. However, the effectiveness of this treatment has not been explored in autochthonous models. We report the efficacy of S. Typhimurium in mice with autochthonous mammary tumors.

MATERIALS AND METHODS

S. Typhimurium attenuated by deletion of cyclic adenosine monophosphate signaling, SalpNG.1, was injected into female BALB-neuT tumor-bearing mice. Mice were monitored for efficacy and sacrificed for mechanistic studies.

RESULTS

In treated mice, seven-week post-treatment tumor burden was reduced by 85% and median survival was increased by 88%. Efficacy was correlated with increased tumor-infiltrating CD8 and natural killer cells. In addition, SalpNG.1 treatment caused a systemic increase of monocytic myeloid-derived suppressor cells that accumulated to high numbers within tumor tissue. Bacteria were not detected in tumor tissue, suggesting that the observed efficacy was due to a systemic rather than a tumor-specific effect of the bacteria.

CONCLUSION

S. Typhimurium treatment reduces tumor burden and increases survival in an autochthonous breast cancer model.

摘要

背景/目的：近年来，用减毒鼠伤寒沙门氏菌治疗癌症的方法越来越受到关注。然而，这种治疗方法在原位模型中的有效性尚未得到研究。我们报告了鼠伤寒沙门氏菌对原位乳腺肿瘤小鼠的疗效。

材料与方法

将通过缺失环磷酸腺苷信号传导减毒的鼠伤寒沙门氏菌SalpNG.1注射到雌性BALB-neuT荷瘤小鼠体内。监测小鼠的疗效，并对其进行处死以进行机制研究。

结果

在接受治疗的小鼠中，治疗后7周肿瘤负担降低了85%，中位生存期延长了88%。疗效与肿瘤浸润性CD8细胞和自然杀伤细胞的增加相关。此外，SalpNG.1治疗导致单核细胞来源的髓系抑制细胞系统性增加，这些细胞在肿瘤组织中大量积累。在肿瘤组织中未检测到细菌，这表明观察到的疗效是由于细菌的全身作用而非肿瘤特异性作用。