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利用 TCR 库:癌症免疫治疗中的预测性见解与治疗监测

英文原题:Harnessing TCR repertoires: predictive insights and therapeutic monitoring in cancer immunotherapy.

查看英文原题

Harnessing TCR repertoires: predictive insights and therapeutic monitoring in cancer immunotherapy.

PubMed 2025/10/01(内容时间) Immunooncol Technol

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中文摘要

T 细胞受体(TCR)库代表了 T 细胞的广泛多样性,是适应性免疫的基石,也是肿瘤学中的有力工具。高通量测序的进步使得能够对 TCR 多样性和克隆性进行深度分析,突显了 TCR 库作为癌症诊断、预后和治疗监测中有前景的生物标志物。本综述综合了当前对 TCR 库分析在癌症诊疗中的理解。肿瘤和外周血中不同的 TCR 特征可以将癌症患者与健康个体区分开来,并有助于疾病分期。在预后方面,聚焦的、克隆性的瘤内 TCR 库通常与改善的生存相关,而外周血中的高多样性通常反映强大的免疫能力和更好的结局。在癌症免疫治疗中,TCR 分析提供了预测性见解;高基线肿瘤克隆性通常与对抗程序性细胞死亡蛋白 1/程序性死亡配体 1 抑制剂的应答相关,而更大的外周多样性可能预测抗细胞毒性 T 淋巴细胞相关蛋白 4(抗 CTLA-4)治疗的获益。动态监测通常显示应答患者的克隆性增加。

此外,TCR 分析对于优化和追踪过继性细胞疗法和癌症疫苗至关重要。尽管具有这种潜力,但重大挑战,包括缺乏方法学标准化,目前限制了广泛的临床应用。将 TCR 分析与多组学和单细胞技术相结合对于克服这些障碍和推进个性化免疫治疗至关重要。

展开英文摘要原文

The T-cell receptor (TCR) repertoire, representing the vast diversity of T cells, is a cornerstone of adaptive immunity and a powerful tool in oncology. Advances in high-throughput sequencing have enabled deep profiling of TCR diversity and clonality, highlighting the repertoire as a promising biomarker for cancer diagnosis, prognosis and therapeutic monitoring. This review synthesizes the current understanding of TCR repertoire analysis in cancer care. Distinct TCR features in tumors and peripheral blood can differentiate cancer patients from healthy individuals and help stage disease.

Prognostically, a focused, clonal intratumoral repertoire is often associated with improved survival, whereas high diversity in peripheral blood typically reflects robust immune competence and better outcomes.

In cancer immunotherapy, TCR profiling offers predictive insights; high baseline tumor clonality frequently correlates with response to anti-programmed cell death protein 1/programmed death-ligand 1 inhibitors, while greater peripheral diversity may predict benefit from anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) therapy. Dynamic monitoring often shows an increase in clonality in patients responding to treatment.

Furthermore, TCR analysis is integral to optimizing and tracking adoptive cell therapies and cancer vaccines. Despite this potential, significant challenges, including a lack of methodological standardization, currently limit widespread clinical application. Integrating TCR analysis with multi-omic and single-cell technologies is essential to overcoming these hurdles and advancing personalized immunotherapy.

论文信息

作者
Chiffelle J、Genolet R、Michielin O、Harari A
单位
Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.Switzerland
文献类型
综述
期刊
Immuno-oncology technology2025 Dec
原文标识
PubMed 41244934 · DOI 10.1016/j.iotech.2025.101076