Quantifiable TCR repertoire changes in prediagnostic blood specimens among patients with high-grade ovarian cancer

Abstract

High-grade 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 enough to detect the microscopic yet metastatic early lesions. In this study, we sequence the blood T cell receptor (TCR) repertoires of 466 patients with ovarian cancer and controls and systematically investigate the immune repertoire signatures in HGOCs. We observe 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 confirm that HGOC signals can be detected in the blood TCR repertoire up to 4 years preceding conventional diagnosis. Our findings may provide the basis for future immune-based HGOC early detection criteria.