Histone deacetylase inhibitors sensitize tumour cells for cytotoxic effects of natural killer cells

Mareike Schmudde, André Braun, Daniela Pende, Jürgen Sonnemann, Ulrike Klier, James F. Beck, Lorenzo Moretta, Barbara M. Bröker

Research output: Contribution to journalArticle

Abstract

Histone deacetylase inhibitors (HDIs) are emerging as potent anti-tumour agents which induce cell cycle arrest, differentiation and/or apoptosis in many tumour cells. Furthermore, they render tumour cells more sensitive to other therapeutic regimens like ionizing radiation, chemotherapy and recombinant tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, we show that the HDIs suberoylanilide hydroxamic acid (SAHA; vorinostat), sodium butyrate (NaB) and MS-275 sensitized DAOY and PC3 tumour cells for the cytotoxic effects of IL-2-activated PBMCs. In 51Cr-release assays, blockade of the activating NK receptors DNAM-1, NKG2D and the NCRs completely abrogated tumour cell lysis, revealing that NK cells were the main effector cells involved. HDIs increased the tumour surface expression of ligands for the activating NK receptors NKG2D and DNAM-1 thereby facilitating tumour cell recognition by NK cells. These results suggest that the combination of HDIs and immunotherapy may be an effective strategy for anti-cancer therapy.

Original languageEnglish
Pages (from-to)110-121
Number of pages12
JournalCancer Letters
Volume272
Issue number1
DOIs
Publication statusPublished - Dec 8 2008

Keywords

  • Histone deacetylase inhibitors
  • NK cells
  • SAHA
  • Sodium butyrate
  • Synergy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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