PO-291 The disbalance of the basic cytokines of the immune system in patients with ovarian cancer on the background of immunotherapy

Abstract

rate. Recent studies indicate that the tumour microenvironment (TME) plays an important role in all stages of tumorigenesis in PaCa. Therefore, both tumour cells and their TME should be targeted for an effective treatment. Eukaryotic elongation factor 2 kinase (EF2K) is an enzyme which is overexpressed in cancer cells and plays a key role in cancer cell survival under stress conditions. There is no study that have shown the relationship between EF2K and TME. Thus, we investigated that the effects of EF2K expression on PaCa cell line (PANC1) and the TME. Material and methods PANC1 cells were cocultured with monocytic THP-1 cells and macrophages were polarised from THP-1 cells. The changes in EF2K expression, cell migration and invasion were analysed using western blot, migration and invasion assays, respectively. The effects of coculture on monocyte chemoattractant protein-1 (MCP-1) levels, which is one of the most important chemokines in TME were analysed using ELISA. The role of MCP-1 on both EF2K and migration of PANC1 cells were investigated. The role of MCP-1 on monocyte-macrophage differentiation was also investigated. To determine the relationship between EF2K and MCP-1, EF2K was stably overexpressed in PANC1 cells and MCP-1 levels were measured using western blot. Then, EF2K was silenced using siRNA and the changes in MCP-1 expression levels, the ability of colony formation, migration and invasion of PANC1 cells were investigated. Pancreatic orthotopic tumour model was used to determine the in vivo effects of EF2K inhibition. In tumour tissues, the changes in expression levels of MCP-1 was measured using western blot and the presence of tumorinfiltrated pro-tumorigenic macrophages were shown using immunohistochemical staining. Results and discussions The interaction between PANC1 cells and macrophages caused an increase in EF2K and MCP-1 proteins and this interaction accelarated cell migration and invasion. In addition, it was found a bidirectional interaction between MCP-1 and EF2K. MCP-1 also caused differentiation of monocytes to pro-tumorigenic macrophages. In vitro silencing of EF2K decreased MCP-1 expression, cell invasion and migration. In vivo inhibition of EF2K also decreased MCP-1 expression, tumour volume and the number of tumor-infiltrated pro-tumorigenic macrophages. Conclusion Targeting both tumour cells and macrohages through EF2K inhibition might be a promising strategy for PaCa treatment. Introduction Cytokines are important players in inflammation, a process highly associated with tumour initiation, tumour growth, angiogenesis and metastasis. Oncostatin M Receptor (OSMR) is a membrane receptor belonging to the interleukin 6 (IL6) receptor family and it has been shown to play a role in inflammation, angiogenesis and tumour progression. In breast cancer it has been associated with the EMT process, key component in cancer progression. While it is clear that cancer cells express the receptor OSMR it seems that the ligand Oncostatin M (OSM) is mainly secreted by the tumour stroma suggesting ...

About the Significance of Cytokine Imbalance in the Pathogenesis of Endometrial Cancer

“…S.V. Kamishov выявил существенные сдвиги баланса между продукцией пронеопластических (IL-6, IFN-a/ß) и антинеопластических (фактор некроза опухоли α) цитокинов у пациенток с раком шейки матки [7].…”