University of Oulu

Honkanen, T.J., Tikkanen, A., Karihtala, P. et al. Prognostic and predictive role of tumour-associated macrophages in HER2 positive breast cancer. Sci Rep 9, 10961 (2019).

Prognostic and predictive role of tumour-associated macrophages in HER2 positive breast cancer

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Author: Honkanen, Tiia J.1,2,3; Tikkanen, Antti1,2,3; Karihtala, Peeter1,2,3;
Organizations: 1Department of Oncology and Radiotherapy, Oulu University Hospital, POB 20, 90029, Oulu, Finland
2Medical Research Center Oulu, POB 5000, 90014, Oulu, Finland
3Cancer and Translational Medicine Research Unit, University of Oulu, POB 5000, 90014, Oulu, Finland
4Department of Pathology, Oulu University Hospital, POB 21, 90029, Oulu, Finland
5Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, 450 Brookline Ave, Boston, MA, 02215, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.5 MB)
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Language: English
Published: Springer Nature, 2019
Publish Date: 2020-04-20


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.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 9
Article number: 10961
DOI: 10.1038/s41598-019-47375-2
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This work was supported by University of Oulu, Oulu University Hospital, Cancer Foundation Finland sr. (J.P.K.) and Ida Montin foundation (T.J.H.).
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