Tumor-associated macrophages in canine visceral hemangiosarcoma

• Published in: Veterinary pathology Vol. 61; no. 1; pp. 32 - 45
• Main Authors: Kerboeuf, Mikael, Haugeberg, Didrik Andreas, Olsen, Tobias, Sørling, Linn Kaia, Koppang, Erling Olaf, Moe, Lars, Haaland, Anita Haug
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-01-2024
• Subjects: Animals; Dog Diseases - pathology; Dogs; Hemangiosarcoma - pathology; Hemangiosarcoma - veterinary; Humans; Immunohistochemistry; Macrophages - pathology; Mice; Oncology; Retrospective Studies; Tumor-Associated Macrophages; immunohistochemistry; cancer model; metastasis; M2; dog; macrophage phenotype
• DOI: 10.1177/03009858231179947
• EISSN: 1544-2217
• ISSN: 0300-9858

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.