Publicação
Impact of anti-CTLA4 and anti-PD1 on the cross talk between cancer and immune cells, underlying CAT-VTE
| datacite.subject.fos | Departamento de Biologia Animal | pt_PT |
| dc.contributor.advisor | Serpa, Jacinta | |
| dc.contributor.advisor | Lopes, Carla Alexandra Mendes | |
| dc.contributor.author | Dias, Catarina de Freitas | |
| dc.date.accessioned | 2024-01-11T10:28:12Z | |
| dc.date.embargo | 2026-10-22 | |
| dc.date.issued | 2023 | |
| dc.date.submitted | 2023 | |
| dc.description | Tese de mestrado, Biologia Humana e Ambiente , 2023, Universidade de Lisboa, Faculdade de Ciências | pt_PT |
| dc.description.abstract | Cancer-associated thrombosis (CAT) and venous thromboembolism (VTE) are frequent cancerrelated complications associated with high mortality, thus the identification of predictive markers urges. Immune checkpoints inhibitors (ICI) used in cancer immunotherapy allow T cell activation against cancer cells. Recent retrospective studies showed increased VTE following ICI administration in some patients. Non-small cell lung cancer (NSCLC) is at high risk of thrombosis and the adoption of immunotherapy as a first line treatment seems to be associated with coagulation-fibrinolysis derangement. In melanoma, a very high-risk of thrombosis disease, few studies have addressed increased risk of coagulation alterations associated to ICI. For this project, we hypothesized that the action of ICI (anti-CTLA4 and anti-PD1) on immune and cancer cells as well as on their interaction, accounts for an increased risk of CAT-VTE. Our goal is to analyze this molecular crosstalk to identify possible prothrombotic biomarkers. We pharmacologically modulated NSCLC and melanoma cell lines in co-culture with CD8+ T cells (T CD8+ ) and Myeloid-Derived Suppressor Cells (MDSC), isolated from healthy blood donors. Immunofluorescence and flow cytometry analyses showed that T CD8+ and ICI increase cancer cell death. The in vitro clotting assay showed that T CD8+ and ICI induce platelet aggregation dependent on the relative quantity of T CD8+ . The Enzyme-Linked Immunosorbent Assay (ELISA) proposed that T CD8+ and ICI differently disrupt Tissue Factor and Podoplanin levels, which were not restored by MDSC exposure. The metabolic remodeling assessment by Nuclear Magnetic Resonance (NMR) suggested differential concentrations of extracellular metabolites upon exposure to T CD8+ and ICI. This study provides some insights about the interplay of immune cells, ICI and cancer cells, influencing the coagulation status. The results obtained constitute a starting point on this theme, denoting the need of further investigation underlying this dynamic, and opening important cues to follow towards the definition of biomarkers. | pt_PT |
| dc.identifier.tid | 203523911 | |
| dc.identifier.uri | http://hdl.handle.net/10451/61729 | |
| dc.language.iso | eng | pt_PT |
| dc.subject | Trombose associada a cancro (CAT) | pt_PT |
| dc.subject | tromboembolismo venoso (VTE) | pt_PT |
| dc.subject | Inibidores de checkpoint imunitários (ICI) | pt_PT |
| dc.subject | Cancro de pulmão de não pequenas células (NSCLC) | pt_PT |
| dc.subject | Melanoma | pt_PT |
| dc.subject | Teses de mestrado - 2023 | pt_PT |
| dc.title | Impact of anti-CTLA4 and anti-PD1 on the cross talk between cancer and immune cells, underlying CAT-VTE | pt_PT |
| dc.type | master thesis | |
| dspace.entity.type | Publication | |
| rcaap.rights | embargoedAccess | pt_PT |
| rcaap.type | masterThesis | pt_PT |
| thesis.degree.name | Tese de mestrado em Biologia Humana e Ambiente | pt_PT |