Immunosequencing identifies signatures of T cell responses for early detection of nasopharyngeal carcinoma

IF 48.8 1区医学 Q1 CELL BIOLOGY

Cancer Cell Pub Date : 2025-05-08 DOI:10.1016/j.ccell.2025.04.009

Shanshan Zhang, Yan Zhou, Zhonghua Liu, Yuqian Wang, Xiang Zhou, Haiwen Chen, Xinyu Zhang, Yanhong Chen, Qisheng Feng, Xiaoping Ye, Shanghang Xie, Mu-Sheng Zeng, Weiwei Zhai, Yi-Xin Zeng, Sumei Cao, Guideng Li, Miao Xu

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Abstract

To identify nasopharyngeal carcinoma (NPC)-relevant T cell receptors (TCRs), we profile the repertoires of peripheral blood TCRβ chains from 228 NPC patients, 241 at-risk controls positive for serum Epstein-Barr virus (EBV) VCA-IgA antibody, and 251 seronegative controls. We develop a TCR-based signature (T-score) based on 208 NPC-enriched CDR3β sequences, which accurately diagnoses NPC in both the original and independent validation cohorts. Notably, a higher T-score, associated with a shorter time interval to NPC diagnosis, effectively identifies early-stage NPC among EBV-seropositive at-risk individuals prior to clinical diagnosis. These NPC-enriched TCRs react against not only EBV-specific antigens but also non-EBV antigens expressed by NPC cells, indicating a broad range of specificities. Moreover, the abundance of NPC-enriched CD8⁺ T cells in blood correlates with the infiltration of non-exhausted T cell counterparts in tumors and predicts prolonged survival, suggesting that these NPC-enriched T cells have significant potential for disease monitoring and therapeutic applications.

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免疫测序鉴定鼻咽癌早期检测的T细胞反应的特征

为了鉴定鼻咽癌（NPC）相关的T细胞受体（TCRs），我们分析了228名鼻咽癌患者、241名血清eb病毒（EBV） VCA-IgA抗体阳性的高危对照者和251名血清阴性对照者的外周血TCRβ链谱。我们基于208个NPC富集的CDR3β序列开发了一个基于tcr的特征（T-score），该特征在原始和独立验证队列中都能准确诊断NPC。值得注意的是，较高的t评分与较短的鼻咽癌诊断时间间隔相关，可以在临床诊断之前有效地识别ebv血清阳性的高危个体中的早期鼻咽癌。这些NPC富集的tcr不仅对ebv特异性抗原起反应，也对NPC细胞表达的非ebv抗原起反应，表明其具有广泛的特异性。此外，血液中富含npc的CD8+ T细胞的丰度与肿瘤中未耗尽的T细胞的浸润相关，并预测了延长的生存期，这表明这些富含npc的T细胞在疾病监测和治疗应用方面具有重大潜力。

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

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.