Wang Lu, Xu Zhiyuan, Zhang Wei, Li Lin, Liu Xiao, Zhang Jing
Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Engineering Medicine & School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, People's Republic of China.
iScience. 2023 Dec 8;27(1):108661. doi: 10.1016/j.isci.2023.108661. eCollection 2024 Jan 19.
Immune receptor repertoire is valuable for developing immunotherapeutic interventions, but remains poorly understood across glioma subtypes including IDH wild type, IDH mutation without 1p/19q codeletion (IDHmut-noncodel) and IDH mutation with 1p/19q codeletion (IDHmut-codel). We assembled over 320,000 TCR/BCR clonotypes from the largest glioma cohort of 913 RNA sequencing samples in the Chinese population, finding that immune repertoire diversity was more prominent in the IDH wild type (the most aggressive glioma). Fewer clonotypes were shared within each glioma subtype, indicating high heterogeneity of the immune repertoire. The TRA-CDR3 was longer in private than in public clonotypes in IDH wild type. CDR3 variable motifs had higher proportions of hydrophobic residues in private than in public clonotypes, suggesting private CDR3 sequences have greater potential for tumor antigen recognition. Finally, we developed GTABdb, a web-based database designed for hosting, exploring, visualizing, and analyzing glioma immune repertoire. Our study will facilitate developing glioma immunotherapy.
免疫受体库对于开发免疫治疗干预措施具有重要价值，但在包括异柠檬酸脱氢酶（IDH）野生型、无1p/19q共缺失的IDH突变（IDHmut-noncodel）和有1p/19q共缺失的IDH突变（IDHmut-codel）在内的胶质瘤亚型中，人们对其了解仍然很少。我们从中国人群中913个RNA测序样本的最大胶质瘤队列中组装了超过320,000个T细胞受体（TCR）/B细胞受体（BCR）克隆型，发现免疫库多样性在IDH野生型（最具侵袭性的胶质瘤）中更为突出。每个胶质瘤亚型内共享的克隆型较少，表明免疫库具有高度异质性。在IDH野生型中，私有克隆型的TRA-CDR3比公共克隆型更长。CDR3可变基序在私有克隆型中比在公共克隆型中具有更高比例的疏水残基，这表明私有CDR3序列具有更大的肿瘤抗原识别潜力。最后，我们开发了GTABdb，这是一个基于网络的数据库，旨在托管、探索、可视化和分析胶质瘤免疫库。我们的研究将有助于开发胶质瘤免疫疗法。
