Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer

Cell
Allen W ZhangSohrab P Shah

Abstract

High-grade serous ovarian cancer (HGSC) exhibits extensive malignant clonal diversity with widespread but non-random patterns of disease dissemination. We investigated whether local immune microenvironment factors shape tumor progression properties at the interface of tumor-infiltrating lymphocytes (TILs) and cancer cells. Through multi-region study of 212 samples from 38 patients with whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T and B cell receptor sequencing, we identified three immunologic subtypes across samples and extensive within-patient diversity. Epithelial CD8+ TILs negatively associated with malignant diversity, reflecting immunological pruning of tumor clones inferred by neoantigen depletion, HLA I loss of heterozygosity, and spatial tracking between T cell and tumor clones. In addition, combinatorial prognostic effects of mutational processes and immune properties were observed, illuminating how specific genomic aberration types associate with immune response and impact survival. We conclude that within-patient spatial immune microenvironment variation shapes intraperitoneal malignant spread, provoking new evolutionary perspectives on HGSC clonal dispers...Continue Reading

Citations

May 18, 2019·CA: a Cancer Journal for Clinicians·Stephanie LheureuxAmit M Oza
Jun 13, 2019·Biology of Reproduction·David P Cook, Barbara C Vanderhyden
Jul 2, 2019·Journal of Leukocyte Biology·Adam J FikeAlison J Carey
Sep 13, 2019·Bioinformatics·Nuraini AguseMohammed El-Kebir
Sep 5, 2019·Cancer Metastasis Reviews·Holger BrongerTobias Dreyer
Oct 3, 2019·Cancers·Theodoulakis ChristofiApostolos Zaravinos
May 16, 2020·American Society of Clinical Oncology Educational Book·Lana E KandalaftGeorge Coukos
Jul 29, 2020·Nature Genetics·Nastaran ZahirChristina Curtis
Sep 10, 2019·Algorithms for Molecular Biology : AMB·Yuanyuan QiMohammed El-Kebir
Sep 15, 2019·Nature Reviews. Cancer·Christine A Iacobuzio-DonahueTravis J Hollman
Aug 8, 2020·Physical Biology·Allen W Zhang, Kieran R Campbell
Oct 2, 2020·PLoS Computational Biology·Leah L WeberMohammed El-Kebir
Nov 7, 2019·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·An CoosemansDirk Timmerman
May 28, 2020·Frontiers in Oncology·Diana Vladimirovna YuzhakovaGeorge Vladimirovich Sharonov
Jul 30, 2020·Cancer Science·Takahiro TsujikawaShigeru Hirano
May 6, 2019·International Journal of Molecular Sciences·Michelle A GlasgowTimothy K Starr
Aug 14, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lana E KandalaftGeorge Coukos
Apr 19, 2019·Proceedings of the National Academy of Sciences of the United States of America·Alex MirandaBrad H Nelson
Jan 17, 2020·Nature Communications·Bojan LosicAugusto Villanueva
Jan 19, 2020·Bulletin of Mathematical Biology·Maximilian A R StroblPhilip K Maini
Jan 16, 2020·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·H-D LiuG Lou
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Yanfei YangXiawei Wei
Jan 6, 2019·Nature Reviews. Drug Discovery·Jérôme Galon, Daniela Bruni
Mar 16, 2019·Nature Reviews. Cancer·Roel G W VerhaakPaul S Mischel
Dec 12, 2019·F1000Research·Oscar MaiquesVictoria Sanz-Moreno
Dec 4, 2019·Nature Reviews. Gastroenterology & Hepatology·Amanda J CraigAugusto Villanueva
Jun 24, 2020·Nature Medicine·Benjamin IzarAviv Regev
Aug 29, 2019·Nature Reviews. Cancer·Johannes G ReiterBert Vogelstein
Mar 31, 2019·Genome Medicine·Matthew W Fittall, Peter Van Loo
Feb 9, 2019·Proceedings of the National Academy of Sciences of the United States of America·Xuefei LiHerbert Levine
Jun 19, 2019·International Journal of Molecular Sciences·Eleonora GhisoniGiorgio Valabrega
May 7, 2019·Annual Review of Genomics and Human Genetics·Marc J WilliamsTrevor A Graham
Mar 22, 2019·Nature·Rachel RosenthalUNKNOWN TRACERx consortium

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