Oncotarget

Research Papers:

Salmonella overcomes tumor immune tolerance by inhibition of tumor indoleamine 2, 3-dioxygenase 1 expression

Yu-Diao Kuan and Che-Hsin Lee _

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Oncotarget. 2016; 7:374-385. https://doi.org/10.18632/oncotarget.6258

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Abstract

Yu-Diao Kuan1, Che-Hsin Lee1,2

1Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung, Taiwan

2Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan

Correspondence to:

Che-Hsin Lee, e-mail: [email protected]

Keywords: salmonella, tumor-targeting, indoleamine 2, 3-dioxygenase 1, immune tolerance

Received: May 31, 2015      Accepted: October 22, 2015      Published: October 28, 2015

ABSTRACT

Over the past decades, Salmonella has been proven capable of inhibiting tumor growth. It can specifically target tumors and due to its facultative anaerobic property, can be more penetrative than other drug therapies. However, the molecular mechanism by which Salmonella inhibits tumor growth is still incompletely known. The antitumor therapeutic effect mediated by Salmonella is associated with an inflammatory immune response at the tumor site and a T cell-dependent immune response. Many tumors have been proven to have a high expression of indoleamine 2, 3-dioxygenase 1 (IDO), which is a rate-limiting enzyme that catalyzes tryptophan to kynurenine, thus causing immune tolerance within the tumor microenvironment. With decreased expression of IDO, increased immune response can be observed, which might be helpful when developing cancer immunotherapy. The expression of IDO was decreased after tumor cells were infected with Salmonella. In addition, Western blot analysis showed that the expression levels of phospho-protein kinase B (P-AKT), phospho-mammalian targets of rapamycin (P-mTOR), and phospho-p70 ribosomal s6 kinase (P-p70s6K) in tumor cells were decreased after Salmonella infection. In conclusion, our results indicate that Salmonella inhibits IDO expression and plays a crucial role in anti-tumor therapy, which might be a promising strategy combined with other cancer treatments.


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