Abstract

Disease outcomes of HER2+ breast cancers have dramatically improved after targeted therapies, such as trastuzumab became available. The main mechanism of action of trastuzumab depends on immunoactivation, while immunosuppressive tumour phenotype has been linked to adverse outcomes. Current study included metastatic HER2+ breast cancer patients treated with trastuzumab (n = 40). Immunohistochemistry was conducted to detect nitric oxide synthase 2 (iNOS) expressing M1 polarized and CD163⁺ M2 polarized macrophages, FoxP3⁺ regulatory T-cells (Tregs), CD47 and indoleamine 2,3-dioxygenase 1 (IDO1). High number of iNOS⁺ M1-like macrophages, both in the center of the tumour (CT) and invasive margin (IM), was significantly associated with improved survival (p = 0.009) while high expression of IDO1 or CD47 in the malignant cells was associated with worsened prognosis (p = 0.018, p = 0.046). High number of CD163⁺ M2-like macrophages in the CT, but not in the IM, and high number of FoxP3⁺ Tregs in both locations showed non-significant tendencies towards poor prognosis. Moreover, high number of iNOS⁺ M1-like macrophages combined with high number of CD8⁺ T-cells in the CT was significantly associated with improved survival (p = 0.0003), and this combined marker predicted patient’s ability to remain progression-free without trastuzumab after responding to the therapy (p = 0.003). Current study highlights the role of M1 polarized macrophages alone and in combination with CD8⁺ cells in HER2+ breast cancer.