Therapeutic benefit of Salmonella attributed to LPS and TNF-α is exhaustible and dictated by tumor susceptibility.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractThe potential of bacteria-mediated tumor therapy (BMTT) is highlighted by more than a century of investigation. Attenuated Salmonella has prevailed as promising therapeutic agents. For BMTT - categorized as an immune therapy - the exact contribution of particular immune reactions to the therapeutic effect remains ambiguous. In addition, one could argue for or against the requirement of bacterial viability and tumor targeting. Herein we evaluate the isolated therapeutic efficacy of purified LPS and TNF-α, which together account for a dominant immunogenic pathway of gram negative bacteria like Salmonella. We show that therapeutic efficacy against CT26 tumors does not require bacterial viability. Analogous to viable Salmonella SL7207, tumor regression by a specific CD8+ T cell response can be induced by purified LPS or recombinant TNF-α (rTNF-α). Conversely, therapeutic effects against RenCa tumors were abrogated upon bacterial avitalization and limited using isolated adjuvants. This argues for an alternative mechanistic explanation for SL7207 against RenCa that depends on viability and persistence. Unable to boost bacterial therapies by co-injection of rTNF-α suggested therapeutic effects along this axis are exhausted by the intrinsic adjuvanticity of bacteria alone. However, the importance of TNF-α for BMTT was highlighted by its support of tumor invasion and colonization in concert with lower infective doses of Salmonella. In consideration, bacterial therapeutic effectiveness along the axis of LPS and TNF-α appears limited, and does not offer the necessary plasticity for different tumors. This emphasizes a need for recombinant strengthening and vehicular exploitation to accommodate potency, plasticity and distinctiveness in BMTT.
CitationTherapeutic benefit of Salmonella attributed to LPS and TNF-α is exhaustible and dictated by tumor susceptibility. 2017, 8 (22):36492-36508 Oncotarget
AffiliationHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- Local application of bacteria improves safety of Salmonella -mediated tumor therapy and retains advantages of systemic infection.
- Authors: Kocijancic D, Felgner S, Schauer T, Frahm M, Heise U, Zimmermann K, Erhardt M, Weiss S
- Issue date: 2017 Jul 25
- Salmonella typhimurium Suppresses Tumor Growth via the Pro-Inflammatory Cytokine Interleukin-1β.
- Authors: Kim JE, Phan TX, Nguyen VH, Dinh-Vu HV, Zheng JH, Yun M, Park SG, Hong Y, Choy HE, Szardenings M, Hwang W, Park JA, Park S, Im SH, Min JJ
- Issue date: 2015
- Innate immunity mediated by MyD88 signal is not essential for induction of lipopolysaccharide-specific B cell responses but is indispensable for protection against Salmonella enterica serovar Typhimurium infection.
- Authors: Ko HJ, Yang JY, Shim DH, Yang H, Park SM, Curtiss R 3rd, Kweon MN
- Issue date: 2009 Feb 15
- Engineered <i>Salmonella enterica</i> serovar Typhimurium overcomes limitations of anti-bacterial immunity in bacteria-mediated tumor therapy.
- Authors: Felgner S, Kocijancic D, Frahm M, Heise U, Rohde M, Zimmermann K, Falk C, Erhardt M, Weiss S
- Issue date: 2018
- Macrophages rapidly internalize their tumor necrosis factor receptors in response to bacterial lipopolysaccharide.
- Authors: Ding AH, Sanchez E, Srimal S, Nathan CF
- Issue date: 1989 Mar 5