Histone deacetylase inhibitors prevent activation of tumour-reactive NK cells and T cells but do not interfere with their cytolytic effector functions

Cancer Lett. 2010 Sep 28;295(2):173-81. doi: 10.1016/j.canlet.2010.02.024. Epub 2010 Mar 25.

Abstract

Histone deacetylase inhibitors (HDIs) exert direct tumour-toxic activity and sensitise tumour cells for other therapeutic regimens as well as the cytotoxic effects of activated immune cells. However, the HDI suberoylanilide hydroxamic acid (SAHA; vorinostat) interfered with the IL-2 activation of human NK cells and the priming of human tumour-specific T cells. In contrast, NK or T cells which were activated in the absence of HDIs became resistant to their immunosuppressive action. Therefore, as a therapeutic strategy, first the patient's immune system might be stimulated and then HDIs could sensitise the tumours for the attack of the pre-activated immune effector cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • B7-2 Antigen / physiology
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic / drug effects*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Interleukin-2 / pharmacology
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation / drug effects*
  • Male
  • Mitomycin / pharmacology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Vorinostat

Substances

  • B7-2 Antigen
  • CD86 protein, human
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Interleukin-2
  • Mitomycin
  • Vorinostat