RRC ID 71798
著者 Gulay KCM, Aoshima K, Maekawa N, Suzuki T, Konnai S, Kobayashi A, Kimura T.
タイトル Hemangiosarcoma cells induce M2 polarization and PD-L1 expression in macrophages.
ジャーナル Sci Rep
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.
巻・号 12(1)
ページ 2124
公開日 2022-2-8
DOI 10.1038/s41598-022-06203-w
PII 10.1038/s41598-022-06203-w
PMID 35136176
PMC PMC8826392
MeSH Animals Cell Line, Tumor Dogs Hemangiosarcoma / immunology Hemangiosarcoma / veterinary* Macrophages / physiology* Mice Splenic Neoplasms / immunology Splenic Neoplasms / veterinary* Tumor Escape* Tumor Microenvironment*
IF 3.998
リソース情報
ヒト・動物細胞 UV♀2(RCB1994) RAW 284(RCB0535)