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Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups
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)...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840469/ https://www.ncbi.nlm.nih.gov/pubmed/33537658 http://dx.doi.org/10.1016/j.isci.2021.102053 |
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author | Lee, Sanghoon Zhao, Li Little, Latasha D. Westin, Shannon N. Jazarei, Amir A. Fleming, Nicole D. Zhang, Jianhua Futreal, P. Andrew Sood, Anil K. |
author_facet | Lee, Sanghoon Zhao, Li Little, Latasha D. Westin, Shannon N. Jazarei, Amir A. Fleming, Nicole D. Zhang, Jianhua Futreal, P. Andrew Sood, Anil K. |
author_sort | Lee, Sanghoon |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7840469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-78404692021-02-02 Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups Lee, Sanghoon Zhao, Li Little, Latasha D. Westin, Shannon N. Jazarei, Amir A. Fleming, Nicole D. Zhang, Jianhua Futreal, P. Andrew Sood, Anil K. iScience Article 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. Elsevier 2021-01-09 /pmc/articles/PMC7840469/ /pubmed/33537658 http://dx.doi.org/10.1016/j.isci.2021.102053 Text en © 2021 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Lee, Sanghoon Zhao, Li Little, Latasha D. Westin, Shannon N. Jazarei, Amir A. Fleming, Nicole D. Zhang, Jianhua Futreal, P. Andrew Sood, Anil K. Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups |
title | Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups |
title_full | Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups |
title_fullStr | Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups |
title_full_unstemmed | Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups |
title_short | Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups |
title_sort | distinct t cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840469/ https://www.ncbi.nlm.nih.gov/pubmed/33537658 http://dx.doi.org/10.1016/j.isci.2021.102053 |
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