Low T cell diversity associates with poor outcome in bladder cancer: A comprehensive longitudinal analysis of the T cell receptor repertoire.

IF 11.7 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2025-05-20 Epub Date: 2025-05-01 DOI:10.1016/j.xcrm.2025.102101

Asbjørn Kjær, Nanna Kristjánsdóttir, Randi Istrup Juul, Iver Nordentoft, Karin Birkenkamp-Demtröder, Johanne Ahrenfeldt, Trine Strandgaard, Deema Radif, Darren Hodgson, Christopher Abbosh, Hugo J W L Aerts, Mads Agerbæk, Jørgen Bjerggaard Jensen, Nicolai J Birkbak, Lars Dyrskjøt

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Abstract

T cells are crucial effector cells in the endogenous defense against cancer, yet the clinical impact of their quantity, diversity, and dynamics remains underexplored. Here, we investigate the clinical relevance of the T cell receptor (TCR) repertoire in patients with bladder cancer. In advanced-stage disease, low pre-treatment peripheral TCR diversity is associated with worse overall survival (p = 0.024), particularly when coupled with low circulating T cell fractions (p = 0.00049). These low-diversity repertoires are dominated by hyper-expanded clones that persist throughout treatment. Further longitudinal analysis reveals reductions in TCR diversity after treatment, indicating adverse effects on the immune system. In early-stage disease, immunotherapy increases TCR diversity in patients with good outcomes. Furthermore, single-cell sequencing identifies most hyper-expanded clones as cytotoxic T cells, while non-expanded clones are predominantly naive T cells. Overall, this highlights TCR diversity as a promising biomarker, offering opportunities for tailored oncological treatments to enhance clinical outcomes.

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低T细胞多样性与膀胱癌预后不良相关：对T细胞受体库的综合纵向分析。

T细胞是内源性抗癌防御中至关重要的效应细胞，但其数量、多样性和动力学的临床影响仍未得到充分研究。在这里，我们研究T细胞受体（TCR）库在膀胱癌患者中的临床相关性。在晚期疾病中，治疗前低的外周TCR多样性与较差的总生存期相关（p = 0.024），特别是当循环T细胞含量低时（p = 0.00049）。这些低多样性的基因库主要是在整个治疗过程中持续存在的超扩展克隆。进一步的纵向分析显示治疗后TCR多样性减少，表明对免疫系统有不良影响。在早期疾病中，免疫治疗可增加患者TCR多样性，预后良好。此外，单细胞测序鉴定大多数超扩增克隆为细胞毒性T细胞，而非扩增克隆主要是幼稚T细胞。总的来说，这突出了TCR多样性作为一个有前途的生物标志物，为量身定制的肿瘤治疗提供了机会，以提高临床结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.