Immune regulatory effects of simvastatin on regulatory T cell-mediated tumour immune tolerance

S. Y. Lee, K. J. Lee, J. Y. Moon, H. K. Choi, H. O. Kim, G. Y. Hur, K. H. Jung, S. Y. Lee, J. H. Kim, C. Shin, J. J. Shim, K. H. In, S. H. Yoo, K. H. Kang

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24 Citations (Scopus)

Abstract

Statins are potent inhibitors of hydroxyl-3-methylglutaryl co-enzyme A (HMG-CoA) reductase, and have emerged as potential anti-cancer agents based on preclinical evidence. In particular, compelling evidence suggests that statins have a wide range of immunomodulatory properties. However, little is known about the role of statins in tumour immune tolerance. Tumour immune tolerance involves the production of immunosuppressive molecules, such as interleukin (IL)-10, transforming growth factor (TGF)- and indoleamine-2,3-dioxygenase (IDO) by tumours, which induce a regulatory T cell (Treg) response. In this study, we investigated the effect of simvastatin on the production of IL-10, TGF- and IDO production and the proliferation of Tregs using several cancer cell lines, and Lewis lung cancer (3LL) cells-inoculated mouse tumour model. Simvastatin treatment resulted in a decrease in the number of cancer cells (3LL, A549 and NCI-H292). The production of the immune regulatory markers IL-10, TGF- in 3LL and NCI-H292 cells increased after treatment with simvastatin. The expression of IDO and forkhead box P3 (FoxP3) transcription factor was also increased in the presence of simvastatin. In a murine 3LL model, there were no significant differences in tumour growth rate between untreated and simvastatin-treated mice groups. Therefore, while simvastatin had an anti-proliferative effect, it also exhibited immune tolerance-promoting properties during tumour development. Thus, due to these opposing actions, simvastatin had no net effect on tumour growth.

Original languageEnglish
Pages (from-to)298-305
Number of pages8
JournalClinical and Experimental Immunology
Volume161
Issue number2
DOIs
Publication statusPublished - 2010 Aug

Keywords

  • indoleamine-2,3-dioxygenase
  • interleukin-10
  • regulatory T cell
  • statin
  • transforming growth factor-β

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Lee, S. Y., Lee, K. J., Moon, J. Y., Choi, H. K., Kim, H. O., Hur, G. Y., Jung, K. H., Lee, S. Y., Kim, J. H., Shin, C., Shim, J. J., In, K. H., Yoo, S. H., & Kang, K. H. (2010). Immune regulatory effects of simvastatin on regulatory T cell-mediated tumour immune tolerance. Clinical and Experimental Immunology, 161(2), 298-305. https://doi.org/10.1111/j.1365-2249.2010.04170.x