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.
Highlights
Bacterial cancer therapy can be traced back to the 19th century: a sarcoma surgeon found that bacterial infection has a beneficial influence on patients with tumors [1]
Salmonella downregulated kynurenine and enhanced the viability of to incubate Jurkat cells (T cells) It has been suggested that kynurenine has the ability to increase T cell apoptosis [27]
We analyze whether Salmonella-mediated decrease of kynurenine in B16F10 and 4T1 has impact on T cell survival
Summary
Bacterial cancer therapy can be traced back to the 19th century: a sarcoma surgeon found that bacterial infection has a beneficial influence on patients with tumors [1]. Salmonella is one bacterium that has been known for years to have proven antitumor efficacy. This species has several advantages that apply to cancer therapy: because it is flagellated, Salmonella can penetrate deeply into tumor tissue yet viruses, drugs and antibodies cannot [6] and because it is a facultative anaerobe, Salmonella can colonize small metastatic and larger tumors [7]. One of the barriers to curing cancer has been tumor immune tolerance, which renders host immunity unable effectively to recognize or kill tumor cells; in some situations, immune cells even undergo inactivation cell cycle arrest and apoptosis [10, 11]. There are some treatments that focus on overcoming this obstacle. 1-methyl tryptophan (1-MT) is an analog of IDO substrate that has a higher affinity and is usually used in combination with chemotherapeutic drugs www.impactjournals.com/oncotarget [17]. 1-MT exist two isoforms, 1-methyl-D-tryptophan (D-1-MT) and 1-methyl-L-tryptophan (L-1-MT)
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