Department of Neurology, University Hospital Zürich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland.
J Neuroimmunol. 2012 Sep 15;250(1-2):27-34. doi: 10.1016/j.jneuroim.2012.05.010. Epub 2012 Jun 9.
Cancer stem cells are an attractive target for immunotherapeutic approaches to glioblastoma. However, an immune inhibitory phenotype of cells currently classified as "glioma-initiating cells" (GIC) might counteract recognition by immune effector cells. Here, we investigate the contribution of the non-classical MHC molecule HLA-E to the immunosuppressive phenotype of GIC. HLA-E is expressed in GIC lines and its expression is reduced upon differentiation of GIC in serum-containing culture conditions. Constitutive HLA-E inhibits natural killer (NK) cell-mediated lysis of GIC since small-interfering RNA-mediated HLA-E gene silencing enhances the immunogenicity of GIC. Increased GIC lysis was observed both in the CD133+ and in the CD133- compartment. Furthermore, the use of interferon-γ as a possible agent to boost an immune response against glioblastoma cells might be limited by the concurrent upregulation of HLA-E.
癌症干细胞是胶质母细胞瘤免疫治疗方法的一个有吸引力的靶点。然而，目前被归类为“神经胶质瘤起始细胞”（GIC）的细胞的免疫抑制表型可能会对抗免疫效应细胞的识别。在这里，我们研究了非经典 MHC 分子 HLA-E 对 GIC 免疫抑制表型的贡献。HLA-E 在 GIC 系中表达，并且其表达在含有血清的培养条件下 GIC 的分化过程中降低。组成性 HLA-E 抑制自然杀伤（NK）细胞介导的 GIC 裂解，因为小干扰 RNA 介导的 HLA-E 基因沉默增强了 GIC 的免疫原性。在 CD133+和 CD133-隔室中均观察到 GIC 裂解增加。此外，干扰素-γ作为一种可能的增强针对神经胶质瘤细胞免疫反应的药物的使用可能受到 HLA-E 同时上调的限制。
