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Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer.
Zhang, Allen W; McPherson, Andrew; Milne, Katy; Kroeger, David R; Hamilton, Phineas T; Miranda, Alex; Funnell, Tyler; Little, Nicole; de Souza, Camila P E; Laan, Sonya; LeDoux, Stacey; Cochrane, Dawn R; Lim, Jamie L P; Yang, Winnie; Roth, Andrew; Smith, Maia A; Ho, Julie; Tse, Kane; Zeng, Thomas; Shlafman, Inna; Mayo, Michael R; Moore, Richard; Failmezger, Henrik; Heindl, Andreas; Wang, Yi Kan; Bashashati, Ali; Grewal, Diljot S; Brown, Scott D; Lai, Daniel; Wan, Adrian N C; Nielsen, Cydney B; Huebner, Curtis; Tessier-Cloutier, Basile; Anglesio, Michael S; Bouchard-Côté, Alexandre; Yuan, Yinyin; Wasserman, Wyeth W; Gilks, C Blake; Karnezis, Anthony N; Aparicio, Samuel; McAlpine, Jessica N; Huntsman, David G; Holt, Robert A; Nelson, Brad H; Shah, Sohrab P.
Afiliação
  • Zhang AW; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada; BC Children's Hospital Research, Vancouver, BC V5Z 4H4, Canada; Graduate Bioinformatics Training Program, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • McPherson A; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Milne K; Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada.
  • Kroeger DR; Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada.
  • Hamilton PT; Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada.
  • Miranda A; Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada.
  • Funnell T; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada; Graduate Bioinformatics Training Program, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Little N; Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada.
  • de Souza CPE; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Laan S; Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada.
  • LeDoux S; Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada.
  • Cochrane DR; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Lim JLP; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Yang W; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Roth A; Department of Statistics, University of Oxford, Oxford OX1 2JD, UK; Ludwig Institute for Cancer Research, University of Oxford, Oxford OX1 2JD, UK.
  • Smith MA; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Ho J; Department of Anatomical Pathology, Vancouver General Hospital, Vancouver, BC V5Z 1M9, Canada.
  • Tse K; Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Zeng T; Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Shlafman I; Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Mayo MR; Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Moore R; Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Failmezger H; Centre for Evolution and Cancer, The Institute of Cancer Research, London SM2 5NG, UK; Division of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UK.
  • Heindl A; Centre for Evolution and Cancer, The Institute of Cancer Research, London SM2 5NG, UK; Division of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UK.
  • Wang YK; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Bashashati A; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Grewal DS; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Brown SD; Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4E6, Canada; Genome Science and Technology Program, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Lai D; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Wan ANC; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Nielsen CB; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Huebner C; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Tessier-Cloutier B; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Anglesio MS; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Bouchard-Côté A; Department of Statistics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Yuan Y; Centre for Evolution and Cancer, The Institute of Cancer Research, London SM2 5NG, UK; Division of Molecular Pathology, The Institute of Cancer Research, London SM2 5NG, UK.
  • Wasserman WW; BC Children's Hospital Research, Vancouver, BC V5Z 4H4, Canada.
  • Gilks CB; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Karnezis AN; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Aparicio S; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • McAlpine JN; Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Huntsman DG; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
  • Holt RA; Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4E6, Canada.
  • Nelson BH; Deeley Research Centre, BC Cancer, Victoria, BC V8R 6V5, Canada; Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8P 3E6, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: bnelson@bccrc.ca.
  • Shah SP; Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: sshah@bccrc.ca.
Cell ; 173(7): 1755-1769.e22, 2018 06 14.
Article em En | MEDLINE | ID: mdl-29754820
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 dispersion.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Linfócitos do Interstício Tumoral Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Cell Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Canadá
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Linfócitos do Interstício Tumoral Tipo de estudo: Prognostic_studies Limite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Cell Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Canadá