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胶质瘤组织中 T 细胞浸润模式的图谱绘制

英文原题:Mapping T cell infiltration patterns in glioma tumor tissue.

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Mapping T cell infiltration patterns in glioma tumor tissue.

PubMed 2025/06/26(内容时间) medRxiv

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研究概要

这些发现强调了在患者临床状况背景下刻画 TCR 库的重要性。这些独特的库特征及相关抗原可能有助于患者预后预测,并作为免疫治疗应用的潜在基础。

研究思路结论见上方概要

胶质瘤免疫组库已成为一个重要的关注点,尤其是在免疫治疗开发背景下,以及作为预后和诊断生物标志物识别的关键因素。

收集了胶质瘤患者的肿瘤组织,并对收集的四种胶质瘤肿瘤亚型中每一种的TIL(肿瘤浸润淋巴细胞)进行了靶向免疫组库测序。根据WHO21分类对胶质瘤进行分层,以绘制星形细胞瘤(II/III级、IV级)、胶质母细胞瘤和少突胶质细胞瘤的TCR图谱。

在对 TCR 库和完整克隆型、V-J 盒及 CDR3 进行分析分层后,我们识别出队列特异性的多样性、克隆型共享和保守性水平。基于 TCR 多样性对这些库进行划分,揭示出对患者生存的显著影响。此外,将 CDR3 结合区域映射至抗原及其来源,突出了预后生物标志物,并识别出与患者临床结局相关的病毒特征结合序列。

展开英文摘要原文

The glioma immune repertoire has emerged as a vital point of interest, particularly in the context of immunotherapeutics development and as a key player for prognostic and diagnostic biomarker identification.

Tumor tissue was collected from glioma patients and targeted immune repertoire sequencing of tumor infiltrating lymphocytes (TIL) from each of the four collected glioma tumor subtypes was performed. Gliomas were stratified based on WHO21 classification to map the TCR landscape of astrocytomas (grade II/III, grade IV), glioblastomas, and oligodendrogliomas.

Following stratification of TCR repertoires and complete clonotype, V-J cassette, and CDR3 analysis, we identified cohort-specific levels of diversity, clonotype sharing, and conservation. Partitioning of these repertoires based on TCR diversity revealed significant influence on patient survival. Furthermore, mapping of CDR3 binding regions to antigens and their origins highlighted prognostic biomarkers and identified sequences binding to viral signatures associated with patient clinical outcomes.

These findings underscore the importance of characterizing TCR repertoires in the context of the patient clinical condition. These unique repertoire signatures and correlated antigens may facilitate patient outcome prognostication and serve as a potential foundation for immunotherapeutic applications.

论文信息

作者
Hsia T、Escobedo AK、Batool SM、Ekanayake E、Dunn GP、Choi BD、Carter BS、Balaj L
单位
Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.United States
文献类型
预印本
期刊
medRxiv : the preprint server for health sciences2025 Jun 26
原文标识
PubMed 40666357 · DOI 10.1101/2025.06.25.25330286