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

Sanghoon Lee; Li Zhao; Latasha D Little; Shannon N Westin; Amir A Jazarei; Nicole D Fleming; Jianhua Zhang; P Andrew Futreal; Anil K Sood

doi:10.1016/j.isci.2021.102053

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

iScience. 2021 Jan 9;24(2):102053. doi: 10.1016/j.isci.2021.102053. eCollection 2021 Feb 19.

Authors

Sanghoon Lee¹, Li Zhao², Latasha D Little², Shannon N Westin³, Amir A Jazarei³, Nicole D Fleming³, Jianhua Zhang², P Andrew Futreal², Anil K Sood³

Affiliations

¹ Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1908, Houston, TX, USA.
² Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³ Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Unit 1362, 1515 Holcombe Boulevard, Houston, TX, USA.

Abstract

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.

Keywords: Biological Sciences; Cancer; Immunology.

Abstract

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