Function of Innate Immune Cells in Breast Cancer
Författare
Summary, in English
In the first project we showed that pro-inflammatory macrophages downregulate estrogen receptor alpha (ERα) on breast cancer cells. We unveiled the molecular mechanism behind this, showing that TNF-α derived from macrophages inactivates transcription factor FOXO3a. Moreover, presence of TAMs in breast cancer tumors associated with ER negativity and worse prognosis in ERα+ patients.
In projects two and three we shifted our focus towards CD169+ macrophages in lymph nodes (LN) and primary tumors (PT) of breast cancer patients. In project II we showed that presence of CD169+ macrophages in metastatic LN correlated with better prognosis, while presence of CD169+ macrophages in PT did not. Association with PD-L1 expression was found in both locations.
In project III we saw that CD169+ TAMs are most likely monocyte derived in a type I IFN environment and display a unique pro-inflammatory phenotype and cytokine profile, but with immunosuppressive function. In a patient cohort they were associated with tertiary lymphoid structures and regulatory T cells, and therefore with worse prognosis.
In conclusion, TAMs represent a broad spectrum of macrophages with unique origin, phenotype, and function. In this thesis we have added to the growing knowledge of these cells and their role in breast cancer. Not only does the type of cancer matter for their function, but further their location and surrounding environment within breast cancer.
Publiceringsår
2021
Språk
Engelska
Publikation/Tidskrift/Serie
Lund University, Faculty of Medicine Doctoral Dissertation Series
Issue
2021:140
Fulltext
- Available as PDF - 10 MB
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Dokumenttyp
Doktorsavhandling
Förlag
Lund University, Faculty of Medicine
Ämne
- Immunology in the medical area
- Cancer and Oncology
Nyckelord
- Tumor associated macrophages
- Breast cancer
- Estrogen receptor alpha
- FOXO3a
- CD169
- PD-L1
- metastatic lymph node
Status
Published
Forskningsgrupp
- Cancer Immunology, Malmö
ISBN/ISSN/Övrigt
- ISSN: 1652-8220
- ISBN: 978-91-8021-147-5
Försvarsdatum
3 december 2021
Försvarstid
09:15
Försvarsplats
Agardh föreläsningssal, CRC, Jan Waldenströms gata 35, Skånes Universitetssjukhus i Malmö. Join by Zoom: https://lu-se.zoom.us/j/61297955930
Opponent
- Charlotta Dabrosin (Professor)