Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, China.
J Neurooncol. 2011 Nov;105(2):149-57. doi: 10.1007/s11060-011-0572-y. Epub 2011 Apr 11.
To explore the immunogenicity of glioma stem-like cell-associated antigens (SAAs) from sorted or unsorted glioma tumor stem-like cells (TSCs) as well as irradiated TSCs. Two primary human malignant glioma lines (SHG62, SHG66) and U87 cell line were primarily cultured in the serum-free medium (SFM) supplemented with EGF/bFGF. TSCs were identified by their self-renewal, multi-lineage differentiation and tumorigenic activity. To prepare SAAs in vitro, CD133+ TSCs were sorted either by magnetic cell sorting or with irradiation (6 Gy).The cytotoxicity induced by autogenous myeloid dendritic cell (DC)-mediated SAA-specific cytotoxic T lymphocytes (CTLs) was assessed by the Just Another Method test. SHG62, SHG66, and U87 cells contained TSCs. CD133+ SAAs-specific CTLs were significantly more cytotoxic than effector cells loaded with unsorted SAA (P < 0.05). Effector cells loaded with irradiated SAAs were more cytotoxic than those with regular SAAs (P < 0.01). SAAs from CD133+ TSCs and irradiated TSCs provide highly immunogenic antigens. TSCs might be a novel source of antigens for DC vaccination against malignant gliomas.
探讨从分选或未分选的神经胶质瘤肿瘤干细胞(TSC)以及辐照 TSC 中提取的神经胶质瘤干细胞相关抗原(SAA)的免疫原性。将两个原发性人恶性神经胶质瘤系(SHG62、SHG66)和 U87 细胞系在含有 EGF/bFGF 的无血清培养基(SFM)中进行初步培养。通过其自我更新、多谱系分化和致瘤活性鉴定 TSC。为了在体外制备 SAA,通过磁细胞分选或辐照(6Gy)分选 CD133+ TSC。通过 Just Another Method 试验评估自体髓样树突状细胞(DC)介导的 SAA 特异性细胞毒性 T 淋巴细胞(CTL)诱导的细胞毒性。SHG62、SHG66 和 U87 细胞均含有 TSC。CD133+ SAA 特异性 CTL 比负载未分选 SAA 的效应细胞具有更高的细胞毒性(P<0.05)。负载辐照 SAA 的效应细胞比负载常规 SAA 的效应细胞具有更高的细胞毒性(P<0.01)。来自 CD133+ TSC 和辐照 TSC 的 SAA 提供了高度免疫原性的抗原。TSC 可能是用于针对恶性神经胶质瘤的 DC 疫苗接种的新型抗原来源。