文章基本信息

标题：Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups
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作者：Sanghoon Lee ; Li Zhao ; Latasha D. Little 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：2
页码：1-38
DOI：10.1016/j.isci.2021.102053
语种：English
出版社：Elsevier
摘要：SummaryIn patients with high-grade serous ovarian cancer (HGSC), it is unclear which genomic features are related to complete gross resection (R0), which is typically associated with better clinical outcomes, or response to neoadjuvant chemotherapy (NACT). In this study, we evaluated T cell receptor (TCR) repertoire diversity in primary and metastatic tumor samples (n = 90) from clinically well-annotated patients with HGSC who achieved R0 or received NACT with excellent or poor response based on a laparoscopic triage algorithm. TCR sequencing followed by an integrative analysis with comprehensive multi-omics data identified higher TCR diversity (e.g., higher number of unique productive sequences and less clonal relatedness) in the R0 than NACT groups. We found enrichment of specificTCRβgenes usage, distinct mutual exclusiveness and co-occurrence pattern ofTCRβgenes among the groups. We also found significantly positive correlations between clonal relatedness and neoantigens, copy number variations, and mutation load in the groups.Graphical abstractDisplay OmittedHighlights•Higher TCR repertoire diversity in the R0versusneoadjuvant chemotherapy groups•Enrichment of specific TCRβ genes usage was noted among HGSC subgroups•Distinct mutual exclusiveness of TCRβ genes was noted among HGSC subgroups•Positive correlations between clonal relatedness and copy number variationsBiological Sciences; Immunology; Cancer