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Complement inhibito...
Complement inhibitor factor H expressed by breast cancer cells differentiates CD14+ human monocytes into immunosuppressive macrophages
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- Smolag, Karolina I. (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Mueni, Christine M. (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Leandersson, Karin (författare)
- Lund University,Lunds universitet,Cancerimmunologi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Cancer Immunology, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Jirström, Karin (författare)
- Lund University,Lunds universitet,Terapeutisk patologi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Therapeutic pathology,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Hagerling, Catharina (författare)
- Lund University,Lunds universitet,Cancercellers evolution,Forskargrupper vid Lunds universitet,Molekylär barnonkologi,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Pathways of cancer cell evolution,Lund University Research Groups,Molecular Pediatric Oncology,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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- Mörgelin, Matthias (författare)
- Colzyx AB
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- Barlow, Paul N. (författare)
- University of Edinburgh
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- Martin, Myriam (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,Protein Chemistry, Malmö,Lund University Research Groups
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- Blom, Anna M. (författare)
- Lund University,Lunds universitet,Proteinkemi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Protein Chemistry, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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(creator_code:org_t)
- 2020
- 2020
- Engelska.
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Ingår i: OncoImmunology. - 2162-4011. ; 9:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Macrophages are a major immune cell type in the tumor microenvironment, where they display a tumor-supporting phenotype. Factor H (FH) is a complement inhibitor that also plays a role in several cellular functions. To date, the phenotype of monocytes stimulated with FH has been unexplored. We discovered that FH is a survival factor for CD14+ primary human monocytes, promoting their differentiation into macrophages in serum-free medium. This activity was localized to the C-terminal domains of FH and it was inhibited in plasma, indicating that the phenomenon may be most relevant in tissues. FH-induced macrophages display characteristics of immunosuppressive cells including expression of CD163 and CD206, release of the anti-inflammatory cytokine IL-10 and changes in metabolism. Furthermore, FH-induced macrophages express low levels of HLA-DR but high levels of co-inhibitory molecule programmed death-ligand 1 (PD-L1), and accordingly, a reduced capacity for T-cell activation. Finally, we show that FH is expressed by human breast cancer cells and that this correlates with the presence of immunosuppressive macrophages, breast cancer recurrence and severity of the disease. We propose that the expression of FH by tumor cells and the promotion of an immunosuppressive cancer microenvironment by this protein should be taken into account when considering the effectiveness of immunotherapies against breast cancer.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Breast cancer
- factor H
- macrophages
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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