Login
Communauté Vinci
Extérieur
Si votre nom d'utilisateur ne se termine pas par @vinci.be ou @student.vinci.be, utilisez le formulaire ci-dessous pour accéder à votre compte de lecteur.
Titre : | Étude du mécanisme daction danticorps anti-GARP:TGF-ß1 dans le contexte de limmunosuppression par les lymphocytes T régulateurs |
Auteurs : | Morgane VANHOORNEWEDER, Auteur ; Grégoire DE STREEL, Promoteur |
Type de document : | Travail de fin d'études |
Editeur : | Bruxelles : Institut Paul Lambin, 2020 |
Langues: | Français |
Index. décimale : | TFE - Biologie médicale |
Résumé : |
Cancer is very present in our society and we would like it to stop. Immunotherapies exist and are based on different mechanisms of cancer development. At de Duve Research Institute, we have been working on one of them to hope to understand how it works and to use it in the best possible way afterwards.
Regulatory T lymphocytes are white blood cells that regulate the immune system by secreting a cytokine from the GARP:TGF-ß1 complex: mature TGF-ß1. The absence of secretion of this protein promotes autoimmune diseases by letting pathological cells expand. However,an excess of secretion causes an inhibition of the anti-tumor immune response and therefore promotes the development of cancers. Sophie Lucas' laboratory has developed antibodies to block this excessive secretion of TGF-ß1. Now we're trying to understand how these antibodies work. For this, different scientific techniques were used such as cell culture, in-vivo injection in mice, flow cytometry in the BD LSR Fortessa instrument and confocal microscopy. To try to answer, two sections were necessary: " demonstration of TGF-ß1 signaling modulation in the tumor microenvironment of mice treated with an anti-GARP-TGF-ß1 antibody " and " mechanism of action of antibodies >GARP:TGF-ß1 to block the release of mature TGF-ß1 ". For the first part, SMAD2 proteins phosphorylating to phosphoSMAD2 and entering the nucleus via a TGF-ß1 signal were used. The proportion of nuclear SMAD2 increases well during fibrosis of spleens, which means that the spleens are fibrotic as a result of modulation of the TGF-ß1 signaling. Also, a screening of the cells present during the development of an in-vivo tumor was performed to obtain a transcriptome reflection after treatment or not with an anti- GARP:TGF-ß1 antibody. For the second part, on the one hand the hypothesis of endocytosis of GARP:TGF-ß1 complexes is rejected because a decrease in the signal linked to the GARP:TGF-ß1 complex is observed when blocking antibodies are added, but this signal has been shown not to be intracellular following the addition of a quencher, a molecule that absorbs the fluorescence emitted by the fluorochromes coupled to the antibodies. On the other hand, confocal microscopy allowed us to observe locations in the cytoplasm where the complexes could be located. The signal emitted by these locations has yet to be quantified. In conclusion, the mechanism of action of anti-GARP:TGF-ß1 antibodies has not been found and needs to be further investigated in the laboratory. |
Accès : | Identifiez-vous avant d'accéder au document électronique |
Disponible en ligne : | Oui |
Lieu du stage : | Institut de recherche de Duve |
Département : | Biologie médicale |
Documents numériques (1)
Ce document n'est visible qu'après identification
TFE biologie médicale Adobe Acrobat PDF |