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Hemangiosarcoma cells induce M2 polarization and PD-L1 expression in macrophages

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Title: Hemangiosarcoma cells induce M2 polarization and PD-L1 expression in macrophages
Authors: Gulay, Kevin Christian M. Browse this author
Aoshima, Keisuke Browse this author
Maekawa, Naoya Browse this author →KAKEN DB
Suzuki, Tamami Browse this author
Konnai, Satoru Browse this author →KAKEN DB
Kobayashi, Atsushi Browse this author
Kimura, Takashi Browse this author →KAKEN DB
Issue Date: 8-Feb-2022
Journal Title: Scientific Reports
Volume: 12
Issue: 1
Start Page: 2124
Publisher DOI: 10.1038/s41598-022-06203-w
Abstract: Hemangiosarcoma (HSA) is a malignant tumor derived from endothelial cells. Tumor-associated macrophages are one of the major components of tumor microenvironment and crucial for cancer development. The presence and function of macrophages in HSA have not been studied because there is no syngeneic model for HSA. In this study, we evaluated two mouse HSA cell lines and one immortalized mouse endothelial cell line for their usefulness as syngeneic models for canine HSA. Our results showed that the ISOS-1 cell line developed tumors with similar morphology to canine HSA. ISOS-1 cells highly expressed KDM2B and had similar KDM2B target expression patterns with canine HSA. Moreover, we determined that in both ISOS-1 and canine HSA tumors, macrophages were present as a major constituent of the tumor microenvironment. These macrophages were positive for CD204, an M2 macrophage marker, and express PD-L1, an immune checkpoint molecule. Canine HSA with macrophages expressing PD-L1 had a smaller number of T-cells in tumor tissues than tumors with PD-L1 negative macrophages. ISOS-1-conditioned medium could induce M2 polarization and PD-L1 expression in RAW264.7 mouse macrophage cell line and mouse peritoneal macrophages. These results show that ISOS-1 can be used as a syngenic model for canine HSA and suggest that macrophages play an important role in immune evasion in HSA. Using the syngeneic mouse model for canine HSA, we can further study the role of immune cells in the pathology of HSA.
Type: article
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 青島 圭佑

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