Grade III canine and feline mammary carcinomas are associated with an immunosuppressed, vascularized and proliferative microenvironment

Abstract Background The tumor immune microenvironment (TIME) of canine and feline mammary carcinomas (CMC and FMC) comprises a complex collection of immune cells that remains underinvestigated. We performed extensive immunohistochemical characterization with specific immune cell markers on retrospectively collected grade I, II and III CMC and FMC to spatially and quantitatively investigate the TIME-associated changes in correlation with the tumor grade, tumor size and necrosis for both species. Results Antigen-presenting cells, tumor-associated macrophages and -neutrophils, were mainly located in the tumoral stroma and formed an immunosuppressive border surrounding the tumor core, most prominently in grade III carcinomas. Activated T lymphocytes were either scattered or clustered in B lymphocyte-rich aggregates in the tumoral stroma, while infiltrated T lymphocytes in the tumor core showed no activation. Grade III mammary carcinomas were characterized by more abundant vascularization compared to grade I/II CMC and FMC. Tumor size, but not necrosis, was identified as influencing factor for both immune cell infiltration and blood vessel density in CMC and FMC. Conclusion Collectively, these data indicate that grade III CMC and FMC are associated with an immunosuppressed, vascularized and proliferative TIME, warranting further exploration of the underlying pro-tumorigenic mechanism for novel prognostic and therapeutic applications in companion animals.