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T细胞受体(TCR)库分析在结直肠癌中的现状

The Current Status of T Cell Receptor (TCR) Repertoire Analysis in Colorectal Cancer.

作者信息

Takahashi Hiroyuki, Hanaoka Katsuzo, Wada Hideo, Kojima Daibo, Watanabe Masato

机构信息

Department of Surgery, Fukuoka University Chikushi Hospital, 1-1-1 Zokumyoin, Chikushino 818-8502, Fukuoka, Japan.

出版信息

Int J Mol Sci. 2025 Mar 17;26(6):2698. doi: 10.3390/ijms26062698.

Abstract

The rapid increase in colorectal cancer (CRC) cases recently has highlighted the need to use predictive biomarkers to guide therapeutic approaches. Current studies have focused on the tumor-infiltrating lymphocytes present in the tumor microenvironment (TME), in which cytotoxic T cell activation and the amount are associated with CRC patient prognosis. The T cell receptor (TCR) is essential for antigen recognition and T cell identification, playing a central role in cancer immunotherapy. The T cell status reflects TCR diversity or clonality, known as the TCR repertoire. Accordingly, analyzing the TCR repertoire dynamics may help predict the immunological circumstances of the TME in a timely way. In this review, we summarize the TCR repertoire-related knowledge, including its potential use as predictive biomarkers in CRC. The intratumoral TCR repertoire is restricted in CRC patients compared with healthy individuals, as well as in peripheral blood. Patients with deficient mismatch repair display more restriction than those with proficient mismatch repair. Importantly, a higher TCR diversity before treatment and a decrease following treatment may indicate a good response and a better clinical outcome in CRC patients. The future use of TCR repertoire sequencing technology combined with artificial intelligence-based analysis is a potential strategy for CRC therapeutic decision making.

摘要

近年来,结直肠癌(CRC)病例的迅速增加凸显了使用预测性生物标志物来指导治疗方法的必要性。目前的研究集中在肿瘤微环境(TME)中存在的肿瘤浸润淋巴细胞,其中细胞毒性T细胞的激活和数量与CRC患者的预后相关。T细胞受体(TCR)对于抗原识别和T细胞识别至关重要,在癌症免疫治疗中发挥着核心作用。T细胞状态反映了TCR的多样性或克隆性,即所谓的TCR库。因此,分析TCR库动态变化可能有助于及时预测TME的免疫情况。在本综述中,我们总结了与TCR库相关的知识,包括其作为CRC预测性生物标志物的潜在用途。与健康个体相比,CRC患者肿瘤内的TCR库以及外周血中的TCR库都受到限制。错配修复缺陷的患者比错配修复功能正常的患者表现出更多的限制。重要的是,治疗前较高的TCR多样性以及治疗后降低可能表明CRC患者有良好的反应和更好的临床结果。未来将TCR库测序技术与基于人工智能的分析相结合的应用是CRC治疗决策的潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6051/11943327/7b1d0e85144b/ijms-26-02698-g001.jpg

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