高级别浆液性卵巢癌（HGOC）是女性死亡的主要原因。早期发现 HGOC 通常可以治愈，但由于超过 90% 的 HGOC 在晚期才被诊断出来，这仍然是一个临床挑战。这主要是因为传统的生物标志物对于检测微小但转移性的早期 HGOC 病变不敏感。在这项研究中，我们对 466 名卵巢癌患者和对照者的血液 T 细胞受体 (TCR) 谱进行了测序，并系统地研究了 HGOC 中的免疫谱特征。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是可重复的。重要的是，这些变化在第一阶段更为强烈。使用来自护士健康研究的诊断前患者血液样本，我们证实，在传统诊断后长达 4 年的时间里，可以在血液 TCR 库中检测到 HGOC 信号。我们的研究结果可能为基于免疫的 HGOC 早期检测标准提供基础。我们取得了前所未有的发现，即在通过常规临床测试诊断高级别卵巢癌之前 4 至 2 年，血液 TCR 库会发生强烈且可量化的变化。这一发现可能有助于开发新的筛查生物标志物来检测早期卵巢癌。

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.We made an unprecedented discovery that a strong and quantifiable change in the blood TCR repertoire occurs 4 to 2 years before high grade ovarian cancers could be diagnosed with conventional clinical tests. This finding might be useful to develop novel screening biomarkers to detect early-stage ovarian cancers.