Wu Xiangyu, Zhao Zihan, Yu Wenhao, Liu Siyang, Zhou Meng, Jiang Ning, Du Xiang, Yang Xin, Chen Jinbang, Guo Hongqian, Yang Rong
Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering Nanjing University, Nanjing 210023, China.
ACS Chem Biol. 2024 Dec 20;19(12):2535-2547. doi: 10.1021/acschembio.4c00635. Epub 2024 Nov 24.
Cancer is a systemic disease continuously monitored and responded to by the human global immune system. Peripheral blood immune cells, integral to this surveillance, exhibit variable phenotypes during tumor progression. Glycosylation, as one of the most prevalent and significant post-translational modifications of proteins, plays a crucial role in immune system recognition and response. Glycan analysis has become a key method for biomarker discovery. LacNAc, a prominent glycosylation modification, regulates immune cell activity and function. Therefore, we applied our previously developed single-cell glycomic multiomics to analyze peripheral blood in cancer patients. This platform utilizes chemoenzymatic labeling with DNA barcodes for detecting and quantifying LacNAc levels at single-cell resolution without altering the transcriptional status of immune cells. For the first time, we systematically integrated single-cell transcriptome, T cell receptor (TCR) repertoire, and glycan epitope LacNAc analyses in tumor-patient-derived peripheral blood. Our integrated analysis reveals that lower-stage bladder cancer patients showed significantly higher levels of LacNAc in peripheral T cells, and peripheral T cells with high levels of cell-surface LacNAc exhibit higher cytotoxicity and TCR clonal expansion. In summary, we identified LacNAc as a potential cell-surface effector marker for peripheral T cells in bladder cancer patients, which enhances our understanding of peripheral immune cells and offers potential advancements in liquid biopsy.
癌症是一种全身性疾病，人体整体免疫系统会持续对其进行监测并做出反应。外周血免疫细胞是这种监测不可或缺的一部分，在肿瘤进展过程中表现出不同的表型。糖基化作为蛋白质最普遍且最重要的翻译后修饰之一，在免疫系统的识别和反应中起着关键作用。聚糖分析已成为发现生物标志物的关键方法。乳糖胺（LacNAc）是一种突出的糖基化修饰，可调节免疫细胞的活性和功能。因此，我们应用我们之前开发的单细胞糖组多组学技术来分析癌症患者的外周血。该平台利用带有DNA条形码的化学酶标记，以单细胞分辨率检测和定量LacNAc水平，同时不改变免疫细胞的转录状态。我们首次在肿瘤患者来源的外周血中系统地整合了单细胞转录组、T细胞受体（TCR）库和聚糖表位LacNAc分析。我们的综合分析表明，低分期膀胱癌患者外周T细胞中的LacNAc水平显著更高，且细胞表面LacNAc水平高的外周T细胞表现出更高的细胞毒性和TCR克隆扩增。总之，我们确定LacNAc是膀胱癌患者外周T细胞潜在的细胞表面效应标志物，这加深了我们对外周免疫细胞的理解，并为液体活检带来了潜在进展。
