Högskolan i Skövde

his.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • apa-cv
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Investigation of immune regulatory mechanisms in myeloid cells: The role of IRAK3 in cancer immune responses
University of Skövde, School of Health Sciences.
2021 (English)Independent thesis Basic level (degree of Bachelor), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

The Interleukin-1 receptor-associated kinase 3 (IRAK3) is a negative regulator of the pro-inflammatory NF-κB signalling pathway. The expression of IRAK3 is localised to monocytes and macrophages, where its expression is associated with an anti-inflammatory M2-macrophage phenotype. While IRAK3 expression is necessary to attenuate acute inflammatory responses, IRAK3 contributes to cancer development by aiding immune evasion and progression. 

The aim of this study was to investigate the effect of IRAK3 in macrophages on their ability to co-stimulate T lymphocytes. CD14+ monocytes and CD3+ T lymphocytes were isolated from fresh buffy coats. CRISPR-Cas9 gene editing technique was employed to knockout IRAK3 in isolated monocytes. Transfected null and IRAK3 knockout macrophages were treated with conditioned media obtained from breast cancer cell lines MCF-7, MDA-MB-231, BT549 and HCC-1937. Conditioned media-treated macrophages were co-cultured with autologous and allogeneic CD3+ T lymphocytes. IFNg and granzyme B concentrations in co-culture supernatants were assessed with ELISA. T lymphocytes were analysed with FACS to immunophenotype and investigate proliferation of CD3+ T lymphocyte sub-populations. 

The study concluded that breast cancer conditioned media induces IRAK3 expression in null macrophages, thus confirming that the anti-inflammatory function of IRAK3 can be exploited by cancer cells via secretion of soluble mediators. Most importantly, IRAK3 knockout macrophages treated with triple negative breast cancer cell line conditioned media exhibited M1 macrophage-like activity by promoting proliferation of effector T cells and their secretion of pro-inflammatory cytokines IFNγ and granzyme B. This observed pro-inflammatory function supports the role of IRAK3 as a possible novel cancer immunotherapy target.

Place, publisher, year, edition, pages
2021. , p. 36
National Category
Biomedical Laboratory Science/Technology
Identifiers
URN: urn:nbn:se:his:diva-19923OAI: oai:DiVA.org:his-19923DiVA, id: diva2:1569711
External cooperation
Yumeng Mao-research group, Uppsala university
Subject / course
Biomedicine/Medical Science
Educational program
Biomedicine - Study Programme
Supervisors
Examiners
Available from: 2021-06-20 Created: 2021-06-20 Last updated: 2021-06-20Bibliographically approved

Open Access in DiVA

No full text in DiVA

By organisation
School of Health Sciences
Biomedical Laboratory Science/Technology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 690 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • apa-cv
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf