The MDM2 inhibitor Nutlin-3 modulates dendritic cell-induced T cell proliferation

Hum Immunol. 2012 Apr;73(4):342-5. doi: 10.1016/j.humimm.2012.01.018. Epub 2012 Feb 13.

Abstract

Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, has been recently taken into consideration as a promising therapeutic tool for tumor treatment based on its ability to stabilize and activate the p53 transcription factor pathway. Since Nutlin-3 displays non cell-autonomous tumor-suppressor activities, we wanted to investigate its effect on dendritic cell functions, given the central role of these cells in the modulation of the immune response. We found that Nutlin-3 alone slightly affected the levels of major histocompatibility complex and costimulatory molecules and significantly promoted the ability of dendritic cells to stimulate T cells in the mixed lymphocyte reaction. Taken together, our findings suggest that the ability of Nutlin-3 to modulate dendritic cell functions and therefore lymphocyte proliferation might represent an additional important mechanism by which Nutlin-3 exerts its non cell-autonomous tumor-suppression function.

MeSH terms

  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Humans
  • Imidazoles / pharmacology*
  • Immunologic Factors / pharmacology*
  • Immunophenotyping
  • Lymphocyte Activation / immunology*
  • Piperazines / pharmacology*
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors*
  • T-Lymphocytes / immunology*

Substances

  • Imidazoles
  • Immunologic Factors
  • Piperazines
  • nutlin 3
  • Proto-Oncogene Proteins c-mdm2