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


Journal

Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332

Informations de publication

Date de publication:
01 04 2021
Historique:
received: 19 02 2021
accepted: 22 02 2021
pubmed: 4 3 2021
medline: 5 2 2022
entrez: 3 3 2021
Statut: ppublish

Résumé

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 single-cell 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.

Identifiants

pubmed: 33653826
pii: dmm.048977
doi: 10.1242/dmm.048977
pmc: PMC8033414
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2021. Published by The Company of Biologists Ltd.

Déclaration de conflit d'intérêts

Competing interests The authors declare no competing or financial interests.

Auteurs

Cara E Wogsland (CE)

Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway.

Hilde E Lien (HE)

Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway.

Line Pedersen (L)

Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway.

Pahul Hanjra (P)

Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway.

Sturla M Grondal (SM)

Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway.

Rolf A Brekken (RA)

Division of Surgical Oncology, Department of Surgery, and Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

James B Lorens (JB)

Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway.

Nils Halberg (N)

Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway.

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Classifications MeSH