Myelodysplastic syndromes (MDS) belong to the most common hematological neoplasms in the elderly population, characterized by ineffective hematopoiesis, peripheral cytopenia and the risk of transformation into acute myeloid leukemia. A dysregulated innate immune response and pro-inflammatory bone marrow microenvironment play a crucial role in the MDS pathogenesis by providing chronic inflammation which makes those pathways the perfect candidate for future therapeutics. Specifically, it has been shown that the alarmin S100A9, an important ligand for dri-ving inflammation and promoting tumor progression, is elevated in MDS patients. Previous expe-riments performed in the Stem Cell Lab 2 provided evidence that mesenchymal stromal cells (MSCs), an important component of the BM niche with immunomodulatory capacity, can be tar-geted by the novel oral small molecular drug Tasquinimod (TASQ, Active Biotech) which has demonstrated S100A9 inhibitory activity. The inhibition of inflammation-related molecules such as IL-1b, IL-18, PD-L1, resulted in a significant improvement of the hematopoietic support by MSCs. However, almost nothing is known about potential effects of TASQ in the context of immunomo-dulation. Therefore, we aimed in this project to understand the mechanisms of S100A9+/- TASQ concerning the immunomodulatory capacity of MDS-MSCs in response to T cell-mediated in-flammation by analyzing adhesion (ICAM1, VCAM1), immune checkpoint (PDL1, PDL2), anti-inflammatory cytokine (COX2, IDO1), chemokines (CCL2, IL8) and extracellular matrix-related (COL4A2, COL1A1) gene expression with quantitative real-time PCR. We observed a general de-crease in the aforementioned genes except for COL4A2 and COL1A1 upon treatment with TASQ, though T cell-mediated inflammation and activity remained unaffected, suggesting that inhibition of S100A9 reduces the inflammation-mediated immunomodulatory potential of MDS-MSCs.:Motivation
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| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:85599 |
| Date | 30 May 2023 |
| Creators | Danismaz, Tolga, Towers, Russell, Baumann, Anna-Lena, Möbus, Kristin, Wobus, Manja |
| Contributors | Technische Universität Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:conferencePoster, info:eu-repo/semantics/conferencePoster, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | urn:nbn:de:bsz:14-qucosa2-855326, qucosa:85532 |
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