@article{8dd52eeb54ff4fc1affbdfa9533215f7,
title = "Distinct T cell receptor repertoire diversity of clinically defined high-grade serous ovarian cancer treatment subgroups",
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",
author = "Sanghoon Lee and Li Zhao and Little, {Latasha D.} and Westin, {Shannon N.} and Jazarei, {Amir A.} and Fleming, {Nicole D.} and Jianhua Zhang and Futreal, {P. Andrew} and Sood, {Anil K.}",
note = "Funding Information: We thank A.M. Sutton (Department of Scientific Publications, The University of Texas MD Anderson Cancer Center, Houston, TX) for editorial assistance. We thank J. Celestino, R.A. Hajek, and M.B. Morgan (MD Anderson Cancer Center, Houston, TX) for their support on the preparation of TCR sequencing. We also acknowledge the MD Anderson Biospecimen Extraction Resource for the extraction of genomic DNA and the MD Anderson Cancer Genomics Laboratory for TCR sequencing. This work was supported in part by the MD Anderson Ovarian Cancer Moon Shot; National Institutes of Health (NIH) grants P50CA217685, R35CA209904 and P30CA016672 (the Clinical Trials Office and Cancer Genomics Laboratory); and the MD Anderson Center for Translational and Public Health Genomics (used the Biospecimen Extraction Resource). S.N.W. is supported by the Andrew Sabin Family Fellowship and the GOG Foundation Scholar Investigator Award. A.K.S. is supported by the American Cancer Society Research Professor Award and the Frank McGraw Memorial Chair in Cancer Research. A.K.S. supervised the study. S.L. P.A.F. and A.K.S. conceived and designed the study. S.L. took the lead in writing the manuscript. S.L. L.Z. and A.K.S. wrote the manuscript. S.L. L.Z. P.A.F. and A.K.S. analyzed, managed and interpreted the sequencing data. L.Z. L.D.L. and J.Z. analyzed and managed the TCR sequencing data. S.L. L.Z. J.Z. P.A.F. and A.K.S. interpreted the TCR sequencing data. S.L. S.N.W. A.A.J. N.D.F. and A.K.S. contributed to the acquisition of clinical samples and data. All authors read and approved the final manuscript. S.N.W. has clinical research grants from AstraZeneca, ArQule, Bayer, Clovis Oncology, Cotinga Pharmaceuticals, NCCN, Novartis, Roche/Genentech, and Tesaro, and consults with AstraZeneca, Circulogene, Clovis Oncology, Merck, Novartis, Pfizer, Roche/Genentech, Takeda, and Tesaro. A.A.J. consults with Roche/Genentech, Aravive, and Almac Group; has research funding from AstraZeneca, Pfizer, Bristol-Myers Squibb, Immatics, and Iovance Biotherapeutics; has honoraria from Gerson Lehrman Group; has travel support from AstraZeneca and MedImmune. N.D.F. consults with Tesaro. A.K.S. consults with Merck and Kiyatec, has research funding from M-Trap, and is a shareholder of Bio-Path Holdings. All other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = feb,
day = "19",
doi = "10.1016/j.isci.2021.102053",
language = "English (US)",
volume = "24",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "2",
}