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黑色素瘤患者的 CD28 T 淋巴细胞具有肿瘤免疫性和高频的胚系编码及公共 TCR。

CD28 T lymphocytes of a melanoma patient harbor tumor immunity and a high frequency of germline-encoded and public TCRs.

机构信息

Department of Pediatric Hematology and Oncology, University Children's Hospital Tuebingen, Hoppe-Seyler Street 1, 72076, Tuebingen, Germany.

出版信息

Immunol Res. 2018 Feb;66(1):79-86. doi: 10.1007/s12026-017-8976-1.

Abstract

Increased numbers of CD8CD28 T cells have been detected in the peripheral blood of patients with several types of malignancies. However, the role of these cells in anticancer immunity are not yet clear and CD8CD28 T cells are a controversially discussed subpopulation reported both as immunosuppressive and cytotoxic. In this study, we examined the T cell receptor (TCR) repertoire and complementarity-determining region 3 sequences of CD28 T cells in a melanoma patient with recurrent disease who achieved long-term disease-free status. As a result, the patient's oligoclonal CD8CD28 T cell compartment holds TCRs that are public and specific for Melan-A as well as several public TCRs reported for common viral antigens. While over 80% of his CD8CD28 T cells expressed a cytotoxicity marker, CD57, only 0.01% of CD8 CD28 T cells were positive for Foxp3. In conclusion, our results demonstrate that besides virus-specific also tumor-associated self-antigen targeting T cells accumulate in the CD28 compartment of the immunological memory. Since the patient is in ongoing complete remission for more than 9 years, CD8CD28 T cells with the Melan-A-specific TCR might contribute to antitumor immunity in this patient.

摘要

在几种类型的恶性肿瘤患者的外周血中已经检测到数量增加的 CD8CD28 T 细胞。然而,这些细胞在抗癌免疫中的作用尚不清楚,CD8CD28 T 细胞是一个备受争议的讨论亚群,既被报道具有免疫抑制作用,也具有细胞毒性作用。在这项研究中,我们研究了一名患有复发性疾病但长期无疾病状态的黑色素瘤患者的 CD28 T 细胞的 T 细胞受体(TCR)库和互补决定区 3 序列。结果表明,患者的寡克隆 CD8CD28 T 细胞群拥有针对 Melan-A 的公共和特异性 TCR,以及针对常见病毒抗原的几种已报道的公共 TCR。虽然他的 80%以上的 CD8CD28 T 细胞表达细胞毒性标志物 CD57,但只有 0.01%的 CD8CD28 T 细胞对 Foxp3 呈阳性。总之,我们的结果表明,除了病毒特异性的 T 细胞外,还会有针对肿瘤相关自身抗原的 T 细胞在免疫记忆的 CD28 群中积累。由于该患者已经持续完全缓解超过 9 年,具有 Melan-A 特异性 TCR 的 CD8CD28 T 细胞可能有助于该患者的抗肿瘤免疫。

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