Abstract 4088: Methylselenic acid inhibits the soluble and cell-surface bound NKG2D-ligand ULBP2 in melanoma

Abstract

Abstract The secretion of the soluble NKG2D-ligand ULBP2 is a marker for poor prognosis in several types of cancer. NKG2D-ligands are normally directed to the cell surface of stressed, inflamed or pre-cancer cells and serve as targets for immune effector cells expressing the NKG2D receptor. The soluble NKG2D-ligands are devastating due to their chronic activation and thereby desensitization of NKG2D expressing immune effector cells. In fact this leads to severely compromised immune activation governing cancer development. The present study describes that methylselenic acid (MSA) is able to inhibit soluble ULBP2 in different primary melanoma cell lines. Moreover, MSA actively suppressed ULBP2 both from constitutively expressing tumors and after induction by HDAC-inhibitors. In the attempt to elucidate the mechanism of inhibition, real-time qPCR experiments were performed. MSA activated the promoter and the transcription of the ULBP2 gene at a level similar to HDAC-inhibitors. These findings strongly indicate that ULBP2 is post-transcriptional regulated. Selective blocking of ULBP2 from melanomas or other cancers that produces soluble immune suppressive ULBP2 is thus a new treatment strategy that also has the potential to be used in combination with existing treatment regimens. Citation Format: Franziska K. Uhlenbrock, Michael Hagemann Jensen, Stephanie Kehlet, Lars Andresen, Søren Skov. Methylselenic acid inhibits the soluble and cell-surface bound NKG2D-ligand ULBP2 in melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4088. doi:10.1158/1538-7445.AM2014-4088