High-dimensional immunotyping of tumors grown in obese and non-obese mice

Cara E. Wogsland, Hilde E. Lien, Line Pedersen, Pahul Hanjra, Sturla M. Grondal, Rolf A. Brekken, James B. Lorens, Nils Halberg

Research output: Contribution to journalArticlepeer-review

Abstract

Obesity is a disease characterized by chronic low-grade systemic inflammation and has been causally linked to the development of 13 cancer types. Several studies have been undertaken to determine whether tumors evolving in obese environments adapt differential interactions with immune cells and whether this can be connected to disease outcome. Most of these studies have been limited to singlecell lines and tumor models and analysis of limited immune cell populations. Given the multicellular complexity of the immune system and its dysregulation in obesity, we applied high-dimensional suspension mass cytometry to investigate how obesity affects tumor immunity. We used a 36-marker immune-focused mass cytometry panel to interrogate the immune landscape of orthotopic syngeneic mouse models of pancreatic and breast cancer. Unanchored batch correction was implemented to enable simultaneous analysis of tumor cohorts to uncover the immunotypes of each cancer model and reveal remarkably model-specific immune regulation. In the E0771 breast cancer model, we demonstrate an important link to obesity with an increase in two T-cell-suppressive cell types and a decrease in CD8 T cells.

Original languageEnglish (US)
Article numberdmm.048977
JournalDMM Disease Models and Mechanisms
Volume14
Issue number4
DOIs
StatePublished - Apr 2021

Keywords

  • Batch correction
  • Breast cancer
  • Obesity
  • Pancreatic cancer
  • Suspension mass cytometry
  • Tumor immunology

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Medicine (miscellaneous)
  • Immunology and Microbiology (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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