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Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
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Hemangiosarcoma cells induce M2 polarization and PD-L1 expression in macrophages
Kevin Christian M Gulay1, Keisuke Aoshima2, Naoya Maekawa3
1Laboratory of Comparative Pathology, Department of Clinical Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan.
Scientific Reports
|February 9, 2022
Summary
A new mouse model (ISOS-1) mimics canine hemangiosarcoma (HSA), revealing tumor-associated macrophages expressing PD-L1. These macrophages contribute to immune evasion, offering a tool to study HSA pathology.
Area of Science:
- Oncology
- Immunology
- Veterinary Medicine
Background:
- Hemangiosarcoma (HSA) is an aggressive cancer originating from endothelial cells.
- Tumor-associated macrophages (TAMs) are key players in cancer development but their role in HSA is unknown due to lack of models.
- No syngeneic model existed for studying canine hemangiosarcoma.
Purpose of the Study:
- To evaluate mouse cell lines as syngeneic models for canine hemangiosarcoma (HSA).
- To investigate the presence and phenotype of macrophages in HSA tumors.
- To explore the role of macrophages in immune evasion within the HSA tumor microenvironment.
Main Methods:
- Assessed three mouse cell lines (two HSA, one endothelial) for suitability as canine HSA models.
- Analyzed tumor morphology, KDM2B expression, and macrophage infiltration in tumors.
- Characterized macrophage markers (CD204, PD-L1) and T-cell presence.
- Used conditioned medium from ISOS-1 cells to assess effects on macrophage polarization and PD-L1 expression.
Main Results:
- The ISOS-1 cell line developed tumors with morphology similar to canine HSA and shared KDM2B expression patterns.
- Macrophages were a major component in both ISOS-1 and canine HSA tumors, expressing M2 marker CD204 and PD-L1.
- Canine HSA tumors with PD-L1-expressing macrophages had fewer T-cells.
- ISOS-1 conditioned medium induced M2 polarization and PD-L1 expression in macrophages.
Conclusions:
- ISOS-1 serves as a valuable syngeneic mouse model for canine HSA research.
- Macrophages expressing PD-L1 are implicated in immune evasion within the HSA tumor microenvironment.
- This model facilitates further investigation into the role of immune cells in HSA pathology.
