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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)843-849
Number of pages7
JournalAnticancer Research
Volume35
Issue number2
StatePublished - Feb 1 2015

Fingerprint

Salmonella enterica
Salmonella typhimurium
Tumor Burden
Breast Neoplasms
Neoplasms
Bacteria
Natural Killer Cells
Cyclic AMP

Keywords

  • Autochthonous model
  • BALB-neuT
  • Breast cancer
  • Cancer therapy
  • Genetically-engineered
  • Immunotherapy
  • Mouse model
  • Myeloid-derived suppressor cells
  • Salmonella

Cite this

Attenuated Salmonella enterica Typhimurium reduces tumor burden in an autochthonous breast cancer model. / Drees, Jeremy; Mertensotto, Michael; Liu, Garvey; Panyam, Jayanth; Leonard, Arnold; Augustin, Lance B; Schottel, Janet L; Saltzman, Daniel A.

In: Anticancer Research, Vol. 35, No. 2, 01.02.2015, p. 843-849.

Research output: Contribution to journalArticle

Drees, Jeremy ; Mertensotto, Michael ; Liu, Garvey ; Panyam, Jayanth ; Leonard, Arnold ; Augustin, Lance B ; Schottel, Janet L ; Saltzman, Daniel A. / Attenuated Salmonella enterica Typhimurium reduces tumor burden in an autochthonous breast cancer model. In: Anticancer Research. 2015 ; Vol. 35, No. 2. pp. 843-849.
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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.",
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