Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer.
- 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
DOIAbstract
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...
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