Phenotypic characterization by mass cytometry of the microenvironment in ovarian cancer and impact of tumor dissociation methods

Shamundeeswari Anandan, Liv Cecilie V. Thomsen, Stein Erik Gullaksen, Tamim Abdelaal, Katrin Kleinmanns, Jørn Skavland, Geir Bredholt, Bjørn Tore Gjertsen, Emmet McCormack, Line Bjørge*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

6 Citations (Scopus)
58 Downloads (Pure)

Abstract

Improved molecular dissection of the tumor microenvironment (TME) holds promise for treating high-grade serous ovarian cancer (HGSOC), a gynecological malignancy with high mortality. Reliable disease-related biomarkers are scarce, but single-cell mapping of the TME could identify patient-specific prognostic differences. To avoid technical variation effects, however, tissue dissociation effects on single cells must be considered. We present a novel Cytometry by Time-of-Flight antibody panel for single-cell suspensions to identify individual TME profiles of HGSOC patients and evaluate the effects of dissociation methods on results. The panel was developed utilizing cell lines, healthy donor blood, and stem cells and was applied to HGSOC tissues dissociated by six methods. Data were analyzed using Cytobank and X-shift and illustrated by t-distributed stochastic neighbor embedding plots, heatmaps, and stacked bar and error plots. The panel distinguishes the main cellular subsets and subpopulations, enabling characterization of individual TME profiles. The dissociation method affected some immune (n = 1), stromal (n = 2), and tumor (n = 3) subsets, while functional marker expressions remained comparable. In conclusion, the panel can identify subsets of the HGSOC TME and can be used for in-depth profiling. This panel represents a promising profiling tool for HGSOC when tissue handling is considered.

Original languageEnglish
Article number755
Pages (from-to)1-18
Number of pages18
JournalCancers
Volume13
Issue number4
DOIs
Publication statusPublished - 2021

Keywords

  • Cell expression profile
  • Characterization
  • Cytometry by Time-of-Flight (CyTOF)
  • High-grade serous ovarian cancer (HGSOC)
  • Single-cell mass cytometry
  • Tumor dissocia-tion
  • Tumor microenvironment (TME)

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