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T 细胞受体链中心性:现象及其在癌症免疫治疗中的潜在应用

英文原题:T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy.

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T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy.

PubMed 2023/10/16(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

T 细胞是适应性抗肿瘤免疫中的关键参与者。用肿瘤抗原特异性 T 细胞受体(TCR)对 T 细胞进行基因修饰是个性化癌症免疫治疗的一个里程碑。TCR 是一种异二聚体(α/β 或 γ/δ),能够识别与自身 MHC 分子形成复合物的肽抗原。尽管传统观点认为 α 链和 β 链对抗原识别的贡献相等,但越来越多的数据表明,某些受体具有链中心性,即一条半链 TCR 主导抗原识别并决定其特异性。目前对链中心性 TCR 的起源及其所表达的功能性 T 细胞亚群了解甚少。此外,α 链中心性和 β 链中心性 TCR 的比例,以及链中心性 TCR 在天然库中的确切比例,至今通常仍不清楚。在这篇综述中,我们对证实链中心性 TCR 的研究进行了回顾性分析,提出了其生成模式,并讨论了此类受体在过继性癌症免疫治疗的 T 细胞基因修饰中的潜在应用。

展开英文摘要原文

T cells are crucial players in adaptive anti-cancer immunity. The gene modification of T cells with tumor antigen-specific T cell receptors (TCRs) was a milestone in personalized cancer immunotherapy. TCR is a heterodimer (either α/β or γ/δ) able to recognize a peptide antigen in a complex with self-MHC molecules.

Although traditional concepts assume that an α- and β-chain contribute equally to antigen recognition, mounting data reveal that certain receptors possess chain centricity, i. e. , one hemi-chain TCR dominates antigen recognition and dictates its specificity. Chain-centric TCRs are currently poorly understood in terms of their origin and the functional T cell subsets that express them.

In addition, the ratio of α- and β-chain-centric TCRs, as well as the exact proportion of chain-centric TCRs in the native repertoire, is generally still unknown today. In this review, we provide a retrospective analysis of studies that evidence chain-centric TCRs, propose patterns of their generation, and discuss the potential applications of such receptors in T cell gene modification for adoptive cancer immunotherapy.

论文信息

作者
Kalinina AA、Khromykh LM、Kazansky DB
单位
N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, 115478 Moscow, Russia.Russia
文献类型
综述
期刊
International journal of molecular sciences2023 Oct 16
原文标识
PubMed 37894892 · DOI 10.3390/ijms242015211