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从TC2N中鉴定出一种新的HLA-A*0201限制性细胞毒性T淋巴细胞表位。

Identification of a new HLA-A*0201-restricted cytotoxic T lymphocyte epitope from TC2N.

作者信息

Yang Zhao, Zhang Hongchuan, Xia Xiaohui, Zhang Jiangwei

机构信息

1Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.

2Department of Oncology, Dianjiang People's Hospital of Chongqing, Chongqing 408300, China.

出版信息

Eur J Microbiol Immunol (Bp). 2024 Feb 15;14(1):59-65. doi: 10.1556/1886.2024.00002. Print 2024 Feb 23.

DOI:10.1556/1886.2024.00002
PMID:38358441
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10895358/
Abstract

Identification of cytotoxic T lymphocyte (CTL) epitopes from tumor related antigens is a promising approach for malignant tumor immunotherapy. TC2N, a recently identified tumor associated antigen from human glioblastoma, is regarded as a promising target of tumor-specific immunotherapy. As one of the most widely used histocompatibility molecules in Chinese is HLA-A0201, we were able to identify the TC2N peptides that are provided by this molecular type. A panel of antigenic peptides produced from TC2N were predicted by using a computer tool. The binding affinities of three peptides with the highest predicted score to the HLA-A0201 molecule were evaluated after synthesis. In vitro and in vivo stimulation of the main T-cell response against the predicted peptides. The results demonstrated that TC2N (152-160) was able to release IFN-γ and lyse U251 cells in vitro as well as in vivo by eliciting peptide-specific CTLs. Our results indicated that peptide TC2N (152-160) (RLYGSVCDL) was a novel HLA-A2.1-restricted CTL epitope capable of inducing TC2N specific CTLs in vitro. As TC2N might qualify as a viable target for immunotherapeutic approaches for patients with GBM, we speculated that the newly identified epitope RLYGSVCDL would be of potential use in peptide-based, cancer-specific immunotherapy against GBM.

摘要

从肿瘤相关抗原中鉴定细胞毒性T淋巴细胞(CTL)表位是恶性肿瘤免疫治疗的一种有前景的方法。TC2N是最近从人胶质母细胞瘤中鉴定出的一种肿瘤相关抗原,被认为是肿瘤特异性免疫治疗的一个有前景的靶点。由于在中国使用最广泛的组织相容性分子之一是HLA-A0201,我们能够鉴定出由这种分子类型呈递的TC2N肽段。利用计算机工具预测了一组由TC2N产生的抗原肽。合成后评估了预测得分最高的三种肽与HLA-A0201分子的结合亲和力。对预测肽段的主要T细胞应答进行体外和体内刺激。结果表明,TC2N(152-160)能够在体外和体内通过引发肽特异性CTL释放IFN-γ并裂解U251细胞。我们的结果表明,肽TC2N(152-160)(RLYGSVCDL)是一种新型的HLA-A2.1限制性CTL表位,能够在体外诱导TC2N特异性CTL。由于TC2N可能是胶质母细胞瘤患者免疫治疗方法的一个可行靶点,我们推测新鉴定的表位RLYGSVCDL在基于肽的、针对胶质母细胞瘤的癌症特异性免疫治疗中具有潜在用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/819939bcaba4/eujmi-14-059-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/5bad4d3bea3a/eujmi-14-059-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/a4f2e7854e97/eujmi-14-059-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/a9aae1ccfe98/eujmi-14-059-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/29a9c5800b32/eujmi-14-059-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/c99b1a6e842f/eujmi-14-059-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/8c2319531f7c/eujmi-14-059-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/819939bcaba4/eujmi-14-059-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/5bad4d3bea3a/eujmi-14-059-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/a4f2e7854e97/eujmi-14-059-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/a9aae1ccfe98/eujmi-14-059-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/29a9c5800b32/eujmi-14-059-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/c99b1a6e842f/eujmi-14-059-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/8c2319531f7c/eujmi-14-059-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de04/10895358/819939bcaba4/eujmi-14-059-g007.jpg

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本文引用的文献

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Tac2-N Promotes Glioma Proliferation and Indicates Poor Clinical Outcomes.Tac2-N 促进神经胶质瘤增殖并预示不良临床结局。
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Identification of TC2N as a novel promising suppressor of PI3K-AKT signaling in breast cancer.鉴定 TC2N 为乳腺癌中新型有前途的 PI3K-AKT 信号通路抑制剂。
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TC2N, a novel oncogene, accelerates tumor progression by suppressing p53 signaling pathway in lung cancer.TC2N 是一种新型癌基因,通过抑制肺癌中的 p53 信号通路加速肿瘤进展。
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