M1 and M2 tumour-associated macrophages subsets in canine malignant mammary tumours: An immunohistochemical study

Abstract

Among the innate and adaptative immune cells recruited to the tumour site, tumour associated macrophages (TAMs) are particularly abundant and by simplified classification can be classified into (M1) and (M2) TAMs. In the present study, we quantified by immunohistochemistry ionized calcium binding adaptor molecule 1 (Iba1)-positive total and CD204-positive M2-polarized TAMs in 60 canine malignant mammary tumours (CMMTs) to analyze the relationship between M1 or M2 response and the histopathologic features of examined CMMTs, the dogs' body condition score (BCS) and the progression of the neoplastic disease. The mean number of total and CD204+ TAMS were significantly higher in solid and in grade III than in grades I and II carcinomas. Moreover, the mean number of CD204-positive TAMs was significantly higher in CMMTs with lymphatic invasion and necrosis rather than CMMTs without. The presence of higher number of CD204-positive M2-polarized TAMs was associated with a worst outcome of the neoplastic disease: bitches bearing CMMTs with a prevalent M2-polarized TAM response had a median cancer-specific survival time of 449 days, while in animals with a M1-polarized TAM response the median cancer-specific survival time was 1209 days. The results of our study confirm that in CMMTs the presence of a M2-polarized TAMs response might affect the tumour development and behaviour. Finally, it strongly suggests the potential of CD204 expression as a prognostic factor.

Keywords: CD204; Canine mammary tumours; Iba1; Immunohistochemistry; M1/M2 TAMs; Prognostic factors.