Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer.
Publication Date
2018-06ICR Author
Author
Zhang, AW
McPherson, A
Milne, K
Kroeger, DR
Hamilton, PT
Miranda, A
Funnell, T
Little, N
de Souza, CPE
Laan, S
LeDoux, S
Cochrane, DR
Lim, JLP
Yang, W
Roth, A
Smith, MA
Ho, J
Tse, K
Zeng, T
Shlafman, I
Mayo, MR
Moore, R
Failmezger, H
Heindl, A
Wang, YK
Bashashati, A
Grewal, DS
Brown, SD
Lai, D
Wan, ANC
Nielsen, CB
Huebner, C
Tessier-Cloutier, B
Anglesio, MS
Bouchard-Côté, A
Yuan, Y
Wasserman, WW
Gilks, CB
Karnezis, AN
Aparicio, S
McAlpine, JN
Huntsman, DG
Holt, RA
Nelson, BH
Shah, SP
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Version of record
Subject
Lymphocytes, Tumor-Infiltrating
Humans
Ovarian Neoplasms
Receptors, Antigen, T-Cell
BRCA1 Protein
BRCA2 Protein
Antigens, Neoplasm
HLA Antigens
Cluster Analysis
Loss of Heterozygosity
Polymorphism, Single Nucleotide
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Young Adult
Neoplasm Grading
Whole Genome Sequencing
CD8 Antigens
Research team
Computational Pathology & Integrated Genomics
Language
eng
Date accepted
2018-03-27
License start date
2018-06
Citation
Cell, 2018, 173 (7), pp. 1755 - 1769.e22