Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups

Abstract

Summary In 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 specific TCRβ genes usage, distinct mutual exclusiveness and co-occurrence pattern of TCRβ genes among the groups. We also found significantly positive correlations between clonal relatedness and neoantigens, copy number variations, and mutation load in the groups.

Molecular Profiles of Serum-Derived Extracellular Vesicles in High-Grade Serous Ovarian Cancer

“…The patient cohort and groups were previously reported [ 5 , 6 ]. In brief, a total of 24 patients were included in this study: nine patients who had no visible residual disease after primary surgery (R0), eight who had an excellent response to NACT (NACT-ER), and seven who had a poor response to NACT (NACT-PR) ( Supplementary Table S1 ).…”

“…Blood samples for 24 patients treated under a systematic surgical algorithm at The University of Texas MD Anderson Cancer Center (Houston, TX, USA) were obtained from the Gynecologic Tumor Bank. The cohort considered for this study was composed of patients with advanced stage ovarian cancer who underwent a laparoscopic assessment to assess primary resectability; the algorithm and patient eligibility were previously described [ 5 , 6 ]. Patients had provided written informed consent under an approved protocol by the Institutional Review Board (LAB10-0850).…”

“…Through comprehensive multi-omics approaches, we have recently discovered significant distinct molecular abnormalities, cellular differences, and immune cell repertoire alterations between highly clinically defined groups of patients who had R0 resection versus those triaged to NACT [ 5 , 6 ]. Our results in tumor specimens point to important underlying biological differences in HGSCs considered resectable versus non-resectable, and in those that respond versus do not respond to NACT.…”

NUF2 promotes tumorigenesis by interacting with HNRNPA2B1 via PI3K/AKT/mTOR pathway in ovarian cancer

“…Ovarian cancer (OC) is the deadliest malignant tumor among female reproductive system diseases, and its mortality rate ranks fifth among all female malignancies [ 1 ]. High-grade serous ovarian cancer (HGSOC) is the most common and aggressive type of OC [ 2 ]. Currently, the standard treatment for OC is surgery combined with chemotherapy.…”

Spatially resolved transcriptomics of high-grade serous ovarian carcinoma

“…We previously attempted a comprehensive multi-omics approach based on bulk transcriptomic, genomic, and proteomic analyses aimed at identifying molecular and cellular differences between responders and non-responders to neoadjuvant chemotherapy (NACT) in a highly clinically annotated dataset ( Lee et al., 2020 , 2021 ). Although differences in copy number variation and T cell infiltration were present between the two groups, these differences were not as extensive as we had anticipated.…”