Yu Xuexin, Ye Jianfeng, Hathaway Cassandra A, Tworoger Shelley, Lea Jayanthi, Li Bo
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia.
Department of Pathology, Perelman School of Medicine, University of Pennsylvania.
bioRxiv. 2023 Oct 17:2023.10.12.562056. doi: 10.1101/2023.10.12.562056.
High grade serous ovarian cancer (HGOC) is a major cause of death in women. Early detection of HGOC usually leads to a cure, yet it remains a clinical challenge with over 90% HGOCs diagnosed at advanced stages. This is mainly because conventional biomarkers are not sensitive to detect the microscopic yet metastatic early HGOC lesions. In this study, we sequenced the blood T cell receptor (TCR) repertoires of 466 ovarian cancer patients and controls, and systematically investigated the immune repertoire signatures in HGOCs. We observed quantifiable changes of selected TCRs in HGOCs that are reproducible in multiple independent cohorts. Importantly, these changes are stronger during stage I. Using pre-diagnostic patient blood samples from the Nurses' Health Study, we confirmed that HGOC signals can be detected in the blood TCR repertoire up to 4 years proceeding conventional diagnosis. Our findings may provide the basis of an immune-based HGOC early detection criterion.
高级别浆液性卵巢癌(HGOC)是女性死亡的主要原因。HGOC的早期检测通常可实现治愈,但它仍是一项临床挑战,超过90%的HGOC在晚期才被诊断出来。这主要是因为传统生物标志物对检测微小但已发生转移的早期HGOC病变不敏感。在本研究中,我们对466名卵巢癌患者和对照组的血液T细胞受体(TCR)库进行了测序,并系统地研究了HGOC中的免疫库特征。我们观察到HGOC中选定TCR的可量化变化,这些变化在多个独立队列中具有可重复性。重要的是,这些变化在I期更为明显。利用护士健康研究中患者诊断前的血液样本,我们证实,在传统诊断前长达4年的时间里,血液TCR库中就能检测到HGOC信号。我们的发现可能为基于免疫的HGOC早期检测标准提供依据。