Cancer and autoimmunity: two sides of the same coin. Complement system proteins in the regulation of immune responses.
Smolag Klosowska, Karolina LU
(2021)
In Lund University, Faculty of Medicine Doctoral Dissertation Series
- Abstract
- Factor H is an inhibitor of the complement system, essential for controlling the alternative pathway and also playing a crucial role in various cellular functions. In this thesis, we identified new intriguing functions of FH as a survival factor for primary human monocytes, promoting their differentiation into immunosuppressive macrophages. We showed that FH is expressed by human breast cancer cells, and that the expression correlates with the presence of immunosuppressive macrophages in the cancer microenvironment, breast cancer recurrence, and severity of the disease. Following this finding, we showed that FH also increases the survival of regulatory T-cells, which is mediated via the binding of FH to the inducible co-stimulator on the... (More)
- Factor H is an inhibitor of the complement system, essential for controlling the alternative pathway and also playing a crucial role in various cellular functions. In this thesis, we identified new intriguing functions of FH as a survival factor for primary human monocytes, promoting their differentiation into immunosuppressive macrophages. We showed that FH is expressed by human breast cancer cells, and that the expression correlates with the presence of immunosuppressive macrophages in the cancer microenvironment, breast cancer recurrence, and severity of the disease. Following this finding, we showed that FH also increases the survival of regulatory T-cells, which is mediated via the binding of FH to the inducible co-stimulator on the surface of the cells. This phenomenon seems to play a role in glioma, an aggressive type of brain tumors, where FH expression positively correlates with the occurrence of regulatory T-cells and a worse prognosis for the patients. In contrast to this detrimental role in cancer, FH was shown to play a beneficial role in the silent removal of apoptotic cells and their remnants. This process is of central importance in the pathogenesis of systemic lupus erythematosus, a severe autoimmune disease. Moreover, we confirmed that a different complement protein, C4d, which is the final cleavage fragment of C4, can be a valuable biomarker to measure the activity of this disease. The loss of sialic acid, an important FH ligand, and diminished binding of FH on platelets and other immune cells was furthermore associated with decreased protection against complement attack in a patient suffering from congenital thrombocytopenia. Altogether this thesis aimed to explore the dual role of complement proteins in cancer and autoimmunity. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/08de70a7-1c3d-4f36-bfc6-c04321e1e482
- author
- Smolag Klosowska, Karolina
LU
- supervisor
-
- Anna Blom LU
- Myriam Martin LU
- opponent
-
- professor Roumenina, Lubka, Université de Paris
- organization
- publishing date
- 2021
- type
- Thesis
- publication status
- published
- subject
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2021:129
- pages
- 83 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Agardh föreläsningssal, CRC, Jan Waldenströms gata 35, Skånes Universitetssjukhus i Malmö
- defense date
- 2021-12-03 13:30:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-136-9
- project
- Factor H in immunology
- language
- English
- LU publication?
- yes
- id
- 08de70a7-1c3d-4f36-bfc6-c04321e1e482
- date added to LUP
- 2021-11-12 11:07:48
- date last changed
- 2022-08-05 08:34:28
@phdthesis{08de70a7-1c3d-4f36-bfc6-c04321e1e482,
abstract = {{Factor H is an inhibitor of the complement system, essential for controlling the alternative pathway and also playing a crucial role in various cellular functions. In this thesis, we identified new intriguing functions of FH as a survival factor for primary human monocytes, promoting their differentiation into immunosuppressive macrophages. We showed that FH is expressed by human breast cancer cells, and that the expression correlates with the presence of immunosuppressive macrophages in the cancer microenvironment, breast cancer recurrence, and severity of the disease. Following this finding, we showed that FH also increases the survival of regulatory T-cells, which is mediated via the binding of FH to the inducible co-stimulator on the surface of the cells. This phenomenon seems to play a role in glioma, an aggressive type of brain tumors, where FH expression positively correlates with the occurrence of regulatory T-cells and a worse prognosis for the patients. In contrast to this detrimental role in cancer, FH was shown to play a beneficial role in the silent removal of apoptotic cells and their remnants. This process is of central importance in the pathogenesis of systemic lupus erythematosus, a severe autoimmune disease. Moreover, we confirmed that a different complement protein, C4d, which is the final cleavage fragment of C4, can be a valuable biomarker to measure the activity of this disease. The loss of sialic acid, an important FH ligand, and diminished binding of FH on platelets and other immune cells was furthermore associated with decreased protection against complement attack in a patient suffering from congenital thrombocytopenia. Altogether this thesis aimed to explore the dual role of complement proteins in cancer and autoimmunity.}},
author = {{Smolag Klosowska, Karolina}},
isbn = {{978-91-8021-136-9}},
issn = {{1652-8220}},
language = {{eng}},
number = {{2021:129}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Cancer and autoimmunity: two sides of the same coin. Complement system proteins in the regulation of immune responses.}},
url = {{https://lup.lub.lu.se/search/files/109630845/e_nailing_ex_karolina.pdf}},
year = {{2021}},
}