巨噬细胞
病理
脾脏
血管肉瘤
免疫组织化学
M2巨噬细胞
转移
生物
癌变
癌症研究
医学
免疫学
癌症
体外
内科学
血管肉瘤
生物化学
作者
Mikael Kerboeuf,Didrik Andreas Haugeberg,Tobias Olsen,Linn Kaia Sørling,Erling Olaf Koppang,Lars Moe,Anita Haug Haaland
标识
DOI:10.1177/03009858231179947
摘要
Canine hemangiosarcoma (HSA) is a highly malignant tumor derived from hematopoietic stem cells and commonly occurs in visceral organs or skin. Visceral HSAs are particularly aggressive and progress rapidly despite multimodal treatment. Tumor-associated macrophages (TAMs) play a central role in carcinogenesis, tumor progression, and metastasis in humans and murine models. In this retrospective study, we investigated the prevalence and phenotype of TAMs in privately owned, treatment-naïve dogs with naturally occurring HSA. We used CD204 as a general macrophage marker and CD206 as a marker for M2-polarized macrophages. Formalin-fixed paraffin-embedded tissues from HSAs in the spleen ( n = 9), heart ( n = 6), and other locations ( n = 12) from 17 dogs were sectioned and immunohistochemically labeled with CD204 and CD206 antibodies. The mean number of log(CD204)- and log(CD206)-positive cells and the ratio of log(CD206/CD204)-positive cells were compared with normal surrounding tissues and between tumor locations. There were significantly more macrophages and M2 macrophages, and a higher ratio of M2 macrophages to total macrophages in tumor hot spots ( P = .0002, P < .0001, and P = .0002, respectively) and in tumor tissues outside of hot spots ( P = .009, P = .002, and P = .007, respectively) than in normal surrounding tissues. There were no significant differences between tumor locations, but there was a trend toward higher numbers of CD204-positive macrophages within the splenic tumors. There was no association between histological parameters or clinical stage and TAM numbers or phenotype. As in humans, TAMs in dogs with HSA have a predominantly M2-skewed phenotype. Dogs with HSA could serve as excellent models to evaluate new TAM-reprogramming therapies.
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