PlumX Metrics
Embed PlumX Metrics

The interface of malignant and immunologic clonal dynamics in high-grade serous ovarian cancer

bioRxiv, ISSN: 2692-8205
2017
  • 1
    Citations
  • 0
    Usage
  • 0
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    1
    • Citation Indexes
      1
      • CrossRef
        1

Article Description

High-grade serous ovarian cancer exhibits extensive intratumoral heterogeneity coupled with widespread intraperitoneal disease. Despite this, metastatic spread of tumor clones is non-random, implying the existence of local microenvironmental factors that shape tumor progression. We interrogated the molecular interface between tumor-infiltrating lymphocytes (TIL) and cancer cells in 143 samples from 21 patients using whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T- and B-cell receptor sequencing. We identify 3 immunologic response categories, which frequently co-exist within individual patients. Furthermore, epithelial CD8+ TIL were inversely associated with malignant cell diversity, evidenced by subclonal neoepitope elimination and spatial tracking between tumor and T-cell clones. Intersecting mutational signatures and immune analysis showed that foldback inversion genomic aberrations lead to worse outcomes even in the presence of cytotoxic TIL (n=433). Thus, regional variation in immune contexture mirrors the pattern of intraperitoneal malignant spread, provoking new perspectives for treatment of this challenging disease.

Bibliographic Details

Zhang, Allen W.; McPherson, Andrew; Milne, Katy; Kroeger, David R.; Hamilton, Phineas T.; Miranda, Alex; Funnell, Tyler; Laan, Sonya; Cochrane, Dawn R.; Lim, Jamie L.P.; Yang, Winnie; Roth, Andrew; Smith, Maia A.; de Souza, Camila; Ho, Julie; Tse, Kane; Zeng, Thomas; Shlafman, Inna; Mayo, Michael R.; Moore, Richard; Failmezger, Henrik; Heindl, Andreas; Wang, Yi Kan; Bashashati, Ali; Brown, Scott D.; Lai, Daniel; Wan, Adrian N. C.; Nielsen, Cydney B.; 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.

Cold Spring Harbor Laboratory

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Immunology and Microbiology; Neuroscience; Pharmacology, Toxicology and Pharmaceutics

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know