TY - JOUR
T1 - Immune environment and antigen specificity of the T cell receptor repertoire of malignant ascites in ovarian cancer
AU - Yoshida-Court, Kyoko
AU - Karpinets, Tatiana V.
AU - Mitra, Aparna
AU - Solley, Travis N.
AU - Dorta-Estremera, Stephanie
AU - Sims, Travis T.
AU - Delgado Medrano, Andrea Y.
AU - El Alam, Molly B.
AU - Ahmed-Kaddar, Mustapha
AU - Lynn, Erica J.
AU - Sastry, K. Jagannadha
AU - Zhang, Jianhua
AU - Futreal, Andrew
AU - Nick, Alpa
AU - Lu, Karen
AU - Colbert, Lauren E.
AU - Klopp, Ann H.
N1 - Funding Information:
A grant from the American Cancer Society project 2457 to Ann Klopp supported the study. The flow studies were performed in the Flow Cytometry and Cellular Imaging Facility, funded partly by the National Cancer Institute Cancer Center Support Grant P30CA16672 to The University of Texas MD Anderson Cancer Center. This funder had no role in study design, data collection, analysis, publication decision, or manuscript preparation.
Publisher Copyright:
© 2023 Yoshida-Court et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2023/1
Y1 - 2023/1
N2 - We evaluated the association of disease outcome with T cell immune-related characteristics and T cell receptor (TCR) repertoire in malignant ascites from patients with high-grade epithelial ovarian cancer. Ascitic fluid samples were collected from 47 high-grade epithelial ovarian cancer patients and analyzed using flow cytometry and TCR sequencing to characterize the complementarity determining region 3 TCR β-chain. TCR functions were analyzed using the McPAS-TCR and VDJ databases. TCR clustering was implemented using Grouping of Lymphocyte Interactions by Paratope Hotspots software. Patients with poor prognosis had ascites characterized by an increased ratio of CD8+ T cells to regulatory T cells, which correlated with an increased productive frequency of the top 100 clones and decreased productive entropy. TCRs enriched in patients with an excellent or good prognosis were more likely to recognize cancer antigens and contained more TCR reads predicted to recognize epithelial ovarian cancer antigens. In addition, a TCR motif that is predicted to bind the TP53 neoantigen was identified, and this motif was enriched in patients with an excellent or good prognosis. Ascitic fluid in high-grade epithelial ovarian cancer patients with an excellent or good prognosis is enriched with TCRs that may recognize ovarian cancer-specific neoantigens, including mutated TP53 and TEAD1. These results suggest that an effective antigen-specific immune response in ascites is vital for a good outcome in high-grade epithelial ovarian cancer.
AB - We evaluated the association of disease outcome with T cell immune-related characteristics and T cell receptor (TCR) repertoire in malignant ascites from patients with high-grade epithelial ovarian cancer. Ascitic fluid samples were collected from 47 high-grade epithelial ovarian cancer patients and analyzed using flow cytometry and TCR sequencing to characterize the complementarity determining region 3 TCR β-chain. TCR functions were analyzed using the McPAS-TCR and VDJ databases. TCR clustering was implemented using Grouping of Lymphocyte Interactions by Paratope Hotspots software. Patients with poor prognosis had ascites characterized by an increased ratio of CD8+ T cells to regulatory T cells, which correlated with an increased productive frequency of the top 100 clones and decreased productive entropy. TCRs enriched in patients with an excellent or good prognosis were more likely to recognize cancer antigens and contained more TCR reads predicted to recognize epithelial ovarian cancer antigens. In addition, a TCR motif that is predicted to bind the TP53 neoantigen was identified, and this motif was enriched in patients with an excellent or good prognosis. Ascitic fluid in high-grade epithelial ovarian cancer patients with an excellent or good prognosis is enriched with TCRs that may recognize ovarian cancer-specific neoantigens, including mutated TP53 and TEAD1. These results suggest that an effective antigen-specific immune response in ascites is vital for a good outcome in high-grade epithelial ovarian cancer.
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U2 - 10.1371/journal.pone.0279590
DO - 10.1371/journal.pone.0279590
M3 - Article
C2 - 36607962
AN - SCOPUS:85145903109
SN - 1932-6203
VL - 18
JO - PloS one
JF - PloS one
IS - 1 January
M1 - e0279590
ER -