Therapeutic Immunology, F79, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Hälsovägen, Huddinge, 14186, Stockholm, Sweden.
Centre for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
Cancer Immunol Immunother. 2018 Feb;67(2):237-246. doi: 10.1007/s00262-017-2066-z. Epub 2017 Oct 20.
The prognosis for patients with glioblastoma is grim. Ex vivo expanded tumor-associated antigen (TAA)-reactive T-cells from patients with glioma may represent a viable source for anticancer-directed cellular therapies. Immunohistochemistry was used to test the survivin (n = 40 samples) and NY-ESO-1 (n = 38 samples) protein expression in tumor specimens. T-cells from peripheral blood were stimulated with TAAs (synthetic peptides) in IL-2 and IL-7, or using a combination of IL-2, IL-15 and IL-21. CD4 and CD8 T-cells were tested for antigen-specific proliferation by flow cytometry, and IFN-γ production was tested by ELISA. Twenty-eight out of 38 cancer specimens exhibited NY-ESO-1 protein expression, 2/38 showed a strong universal (4+) NY-ESO-1 staining, and 9/40 cancer lesions exhibited a strong (4+) staining for survivin. We could detect antigen-specific IFN-γ responses in 25% blood samples for NY-ESO-1 and 30% for survivin. NY-ESO-1-expanded T-cells recognized naturally processed and presented epitopes. NY-ESO-1 or survivin expression in glioma represents viable targets for anticancer-directed T-cells for the biological therapy of patients with glioma.
胶质母细胞瘤患者的预后较差。从胶质瘤患者中体外扩增的肿瘤相关抗原 (TAA)-反应性 T 细胞可能代表用于抗癌定向细胞治疗的可行来源。免疫组织化学用于检测肿瘤标本中的生存素 (n=40 个样本) 和 NY-ESO-1 (n=38 个样本) 蛋白表达。外周血中的 T 细胞在 IL-2 和 IL-7 中用 TAA（合成肽）刺激，或使用 IL-2、IL-15 和 IL-21 的组合刺激。通过流式细胞术测试 CD4 和 CD8 T 细胞的抗原特异性增殖，通过 ELISA 测试 IFN-γ 的产生。38 个癌症标本中有 28 个显示 NY-ESO-1 蛋白表达，38 个中有 2 个显示强烈的普遍 (4+) NY-ESO-1 染色，40 个癌症病变中有 9 个显示强烈的 (4+)生存素染色。我们可以在 25%的 NY-ESO-1 血液样本和 30%的生存素血液样本中检测到抗原特异性 IFN-γ 反应。NY-ESO-1 扩增的 T 细胞识别天然加工和呈递的表位。NY-ESO-1 或生存素在胶质瘤中的表达代表了用于治疗胶质瘤患者的抗癌定向 T 细胞的生物治疗的可行靶标。
