Immune Cell Profiles of Metastatic HER2 Positive Breast Cancer Patients According To The Sites of Metastasis

Abstract

Purpose: Recent works have characterized that metastatic site can affect the tumour immune profiles and efficiency of cancer immunotherapies. The prognosis of HER2 positive breast cancer is associated with the characteristics of the tumour immune microenvironment, with immunological cells playing a central role in efficiency of HER2 targeted antibodies. Here we investigated the prognostic significance of different metastatic sites and their correlation to tumour immune profiles in HER2 positive breast cancer treated with trastuzumab. Methods: We collected all (n=54) HER2 positive metastatic breast cancer patients treated with trastuzumab containing regimens at Oulu University Hospital 2009-2014. Pathological and clinical data were collected from electronic patient records. The tumour immune profiles were analysed from pre-treatment primary tumours using well-characterized immunological markers with computer-assisted immune cell counting. Results: Of the metastatic sites, only liver metastases were associated with poor prognosis (hazard ratio 1.809, 95% confidence interval 1.004 – 3.262), especially when presenting as the primary site of metastases. Of the other sites, pulmonary metastases characterized a patient profile with trend to improved survival. Of the studied tumour immunological markers, liver metastases had low densities of CD3+ T-cells (p=0.030) and M1-like macrophages in their primary tumours (p=0.025). Of the other studied markers and sites, pulmonary metastases had low STAB1+ immunosuppressive macrophage density in their primary tumours.Conclusions: Our results suggest that the site of metastasis is associated with prognosis in HER2 positive breast cancer, highlighted by the poor prognosis of liver metastases. Furthermore, liver metastases were associated with adverse tumour immune cell profiles.

Reprogramming tumor-associated macrophages as a unique approach to target tumor immunotherapy

“…Overall survival and metastasis-free survival are improved when they are present in various tumor forms, including osteosarcoma and esophageal cancers (71-73). In contrast, macrophages are linked to a poorer prognosis in some malignancies, especially when paired with a lack of CD8+ cells (74)(75)(76)(77), the type of lymphocyte responsible for destroying tumor cells.…”