Ionizing Radiation Alters the Expression of Multifunctional Immune-Modulatory Protein HLA-E in Glioblastoma Cells Lines: An Unrecognized Effect of Radiation Therapy?
Leos Kren, Ondrej Slaby, Sabina Sevcikova, Lenka Kubiczkova, Martin Smrcka. University Hospital Brno, Brno, Czech Republic; Masaryk Memorial Cancer Institute, Brno, Czech Republic; Medical College, University of Masaryk, Brno, Czech Republic
Background: Immune-modulatory proteins HLA-G and HLA-E were originally thought to be restricted to the protection of the fetus from maternal allorecognition. Now they are known for multiple immune-regulatory functions. We already described production of immune-modulatory molecules HLA-G and HLA-E by both microglial cells (Kren, L. et al., J Neuroimmunol 2010) and neoplastic cells (Kren, L. et al. Neuropathology 2011). We described the unexpected positive correlation of HLA-E expression by neoplastic cells in glioblastoma (GB) with the length of survival, which we hypothetized could be attributable to subsequent therapeutic modalities. Therefore, we decided to analyse the expression of HLA-G and HLA-E in three GB cell lines before and after the impact of ionizing radiation.
Design: We used three GB cell lines: T 98G, A172 and U 87MG. The expression of HLA-G and HLA-E was assessed before application of ionizing radiation (0-2-5-10-15-20 Gy) and then was analysed again 24h and 72 h after radiation. HLA-G and HLA-E antigens were analysed flow-cytometrically.
Results: The expression of both HLA-G and HLA-E by all three cell lines of GB was elevated significantly after irradiation, expecially expression of HLA-E in the line T 98G.
Conclusions: We revealed that expression of HLA-G and HLA-E in GB cell lines alters significantly after the impact of ionizing radiation. This finding may represent a new, unrecognized pathway of the effect of ionizing radiation in cancer therapy. In GB, namely, HLA-E may function, in its elevated levels, as a ligand for activating receptor CD94/NKG2C, therefore mediating increased lysis of tumor cells.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 251, Tuesday Afternoon