近日，中山大学教授徐淼及其研究小组报道了免疫测序鉴定鼻咽癌早期检测的T细胞反应的特征。相关论文于2025年5月8日发表在《癌细胞》杂志上。

为了鉴定鼻咽癌（NPC）相关T细胞受体（TCRs），该课题组研究人员分析了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。该课题组人员基于208个NPC富集的CDR3β序列开发了一个基于TCRs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TCRs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非衰竭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。

附：英文原文

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

Author: 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

Issue&Volume: 2025-05-08

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.

DOI: 10.1016/j.ccell.2025.04.009

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00168-0