Ueda Ryo, Low Keri L, Zhu Xinmei, Fujita Mitsugu, Sasaki Kotaro, Whiteside Theresa L, Butterfield Lisa H, Okada Hideho
Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
J Transl Med. 2007 Dec 19;5:68. doi: 10.1186/1479-5876-5-68.
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.
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 alpha2 subunit (IL-13Ralpha2) by immunohistochemistry.
The patient's tumor expressed both EphA2 and IL-13Ralpha2, and in vitro stimulated PBMC demonstrated superior EphA2883-891 and IL-13Ralpha2345-353-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.
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.
在高级别胶质瘤患者中，关于针对胶质瘤相关抗原（GAA）的天然适应性T细胞反应性的存在情况知之甚少。在本报告中，我们对一名间变性星形细胞瘤（AA）存活超过12年且无复发的患者的GAA特异性CD8 + T细胞和先天免疫细胞进行了特征分析。
评估了来自AA长期存活者的外周血单个核细胞（PBMC）中识别GAA衍生表位的CD8 +细胞的频率、细胞毒性T淋巴细胞（CTL）活性和分化状态，以及其他免疫细胞亚群的相对数量。通过免疫组织化学评估了该患者AA组织中两种GAA EphA2和白细胞介素-13受体α2亚基（IL-13Rα2）的表达。
该患者的肿瘤表达了EphA2和IL-13Rα2，与另外两名进展性恶性胶质瘤患者的PBMC样本相比，体外刺激的PBMC表现出更强的EphA2883 - 891和IL-13Rα2345 - 353特异性CTL反应性。未刺激的EphA2883 - 891反应性CD8 + T细胞包含大量CD45RA - /CCR7 - 晚期效应细胞和CD45RA - /CCR7 + 中央记忆细胞。在其他白细胞亚群中，发现NK - T细胞数量增加。
据我们所知，当前研究是首批证明在一名AA存活超过12年且无复发的患者中存在抗原经验丰富的、GAA反应性CD8 + T细胞的研究之一。有必要进一步研究以确定GAA反应性CD8 + T细胞的状态是否决定患者的生存和/或对治疗性疫苗的反应。
