The development of new biomarkers or therapeutic targets for cancer immunotherapies requires deep understanding of T cells. To date, the complete landscape and systematic characterization of long noncoding RNAs (lncRNAs) in T cells in cancer immunity are lacking. Here, by systematically analyzing full-length single-cell RNA sequencing (scRNA-seq) data of more than 20,000 libraries of T cells across three cancer types, we provided the first comprehensive catalog and the functional repertoires of lncRNAs in human T cells. Specifically, we developed a custom pipeline for de novo transcriptome assembly and obtained a novel lncRNA catalog containing 9433 genes. This increased the number of current human lncRNA catalog by 16% and nearly doubled the number of lncRNAs expressed in T cells. We found that a portion of expressed genes in single T cells were lncRNAs which had been overlooked by the majority of previous studies. Based on metacell maps constructed by the MetaCell algorithm that partitions scRNA-seq datasets into disjointed and homogenous groups of cells (metacells), 154 signature lncRNA genes were identified. They were associated with effector, exhausted, and regulatory T cell states. Moreover, 84 of them were functionally annotated based on the co-expression networks, indicating that lncRNAs might broadly participate in the regulation of T cell functions. Our findings provide a new point of view and resource for investigating the mechanisms of T cell regulation in cancer immunity as well as for novel cancer-immune biomarker development and cancer immunotherapies.

为癌症免疫疗法开发新的生物标志物或治疗靶点需要对 T 细胞有深入的了解。迄今为止，缺乏癌症免疫中 T 细胞中长链非编码 RNA (lncRNA) 的完整景观和系统表征。在这里，通过系统分析三种癌症类型的 20,000 多个 T 细胞文库的全长单细胞 RNA 测序 (scRNA-seq) 数据，我们提供了第一个全面的目录和人类 T 细胞中 lncRNA 的功能库。具体来说，我们为从头 转录组组装开发了一个定制管道并获得了包含9433个基因的新型lncRNA目录。这将当前人类 lncRNA 目录的数量增加了 16%，并使 T 细胞中表达的 lncRNA 数量增加了近一倍。我们发现在单个 T 细胞中表达的基因的一部分是 lncRNA，这在之前的大多数研究中都被忽视了。基于元细胞由 MetaCell 算法构建的图谱将 scRNA-seq 数据集划分为不连贯且同质的细胞组（元细胞），鉴定了 154 个特征 lncRNA 基因。它们与效应、耗尽和调节 T 细胞状态有关。此外，其中 84 个基于共表达网络进行了功能注释，表明 lncRNA 可能广泛参与 T 细胞功能的调节。我们的研究结果为研究 T 细胞在癌症免疫中的调控机制以及新型癌症免疫生物标志物的开发和癌症免疫疗法提供了新的视角和资源。