Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer
| Autor: | Andreas Heindl, Yinyin Yuan, Brad H. Nelson, Allen W. Zhang, Samuel Aparicio, Ali Bashashati, Richard D. Moore, Yi Kan Wang, Daniel Lai, Tyler Funnell, Thomas Zeng, Winnie Yang, Camila P. E. de Souza, David G. Huntsman, Wyeth W. Wasserman, Alexandre Bouchard-Côté, Anthony N. Karnezis, Andrew McPherson, Dawn R. Cochrane, Jessica N. McAlpine, Scott D. Brown, Katy Milne, Maia A. Smith, C. Blake Gilks, David R. Kroeger, Stacey Ledoux, Robert A. Holt, Michael Mayo, Alex Miranda, Kane Tse, Henrik Failmezger, Julie Ho, Sonya Laan, Sohrab P. Shah, Adrian Wan, Basile Tessier-Cloutier, Cydney B. Nielsen, Inna Shlafman, Andrew Roth, Curtis Huebner, Diljot Grewal, Michael S. Anglesio, Jamie L. P. Lim, Nicole S. Little, Phineas T. Hamilton |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult T cell CD8 Antigens Receptors Antigen T-Cell Loss of Heterozygosity Human leukocyte antigen Biology Somatic evolution in cancer Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Young Adult Immune system Lymphocytes Tumor-Infiltrating Antigens Neoplasm HLA Antigens medicine Cluster Analysis Humans Aged Aged 80 and over BRCA2 Protein Ovarian Neoplasms Whole Genome Sequencing Tumor-infiltrating lymphocytes BRCA1 Protein Middle Aged medicine.disease 3. Good health 030104 developmental biology medicine.anatomical_structure Tumor progression Cancer research Female Neoplasm Grading Clone (B-cell biology) Ovarian cancer |
| Zdroj: | Cell. 173(7) |
| ISSN: | 1097-4172 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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