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首页> 外文期刊>Journal of Translational Medicine >Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant glioma
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Spontaneous immune responses against glioma-associated antigens in a long term survivor with malignant glioma

机译:具有恶性胶质瘤的长期幸存者中对胶质瘤相关抗原的自发免疫反应

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Background In patients with high grade glioma, little is known regarding existence of naturally occurring adaptive T cell reactivity against glioma-associated antigens (GAAs). In this report, we characterized GAA-specific CD8+ T cells and innate immune cells in a patient who has survived with anaplastic astrocytoma (AA) for over 12 years without recurrence. Methods Peripheral blood mononuclear cells (PBMCs) derived from the long term survivor with AA were evaluated for the frequency, cytotoxic T lymphocyte (CTL) activity and differentiation status of CD8+ cells recognizing GAA-derived epitopes as well as relative numbers of other immune cell subsets. This patient's AA tissue was evaluated for expression of two GAAs EphA2 and interleukin-13 receptor α2 subunit (IL-13Rα2) by immunohistochemistry. Results The patient's tumor expressed both EphA2 and IL-13Rα2, and in vitro stimulated PBMC demonstrated superior EphA2883–891 and IL-13Rα2345–353-specific CTL reactivity compared to PBMC samples from two other patients with progressing malignant glioma. Unstimulated EphA2883–891-reactive CD8+ T cells contained high numbers of CD45RA-/CCR7- late effector and CD45RA-/CCR7+ central memory cells. Among other leukocyte subsets, elevated numbers of NK-T cells were found. Conclusion To our knowledge, the current study is one of the first demonstrating the presence of antigen-experienced, GAA-reactive CD8+ T cells in a patient who has survived with AA for over 12 years without recurrence. Further studies are warranted to determine whether the status of GAA-reactive CD8+ T cells dictates survival of patients and/or response to therapeutic vaccines.
机译:在高级胶质瘤患者中的背景,关于存在对胶质瘤相关抗原的天然存在的自适应T细胞反应性(GaAs)的存在而少知。在本报告中,我们在患者中表征了GAA特异性CD8 + T细胞和先天免疫细胞,其患有血吸虫细胞瘤(AA)超过12年的患者,无需复发。方法对具有AA的长期幸存流体的外周血单核细胞(PBMCs)对CD8 + 细胞的频率,细胞毒性T淋巴细胞(CTL)活性和分化状态也符合GaA衍生的表位的细胞作为其他免疫细胞亚群的相对数量。通过免疫组织化学评价该患者的AA组织的表达两种GaAs Epha2和白细胞介素-13受体α2亚基(IL-13Rα2)。结果患者的肿瘤表达Epha2和IL-13Rα2,并且体外刺激的PBMC证明了优异的Epha2 883-891 和IL-13Rα2 345-353相比之下的CTL反应性。来自另外两名患者的PBMC样品进行恶性胶质瘤。未刺激的Epha2 883-891 - 反应性CD8 + T细胞包含高量的CD45ra - / ccr7 - 后效应器和CD45ra - / ccr7 + 中央存储器单元。在其他白细胞亚组中,发现了升高的NK-T细胞。结论到我们的知识,目前的研究是第一次证明抗原经验丰富的GAA反应性CD8 + T细胞中的患者在患者中,在没有复发的情况下在没有复发的情况下存活过12岁以上。有必要进一步研究来确定GaA反应性CD8 + T细胞的状态是否决定了患者的存活和/或对治疗疫苗的反应。

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