{"id":{"repo_id":"sherbrooke","oai_identifier":"oai:usherbrooke.scholaris.ca:11143/21815"},"canonical_url":"https://search.dev.ndltd.org/etd/sherbrooke/oai:usherbrooke.scholaris.ca:11143/21815","repository":{"repo_id":"sherbrooke","name":"Université de Sherbrooke","base_url":"https://usherbrooke.scholaris.ca/server/oai/request"},"display":{"title":"Étude de l’expression et du rôle du ligand du co-stimulateur inductible des cellules T (ICOSL) dans les ostéoclastes humains","abstract":"When cancer cells metastasize to bone, they interact in the bone microenvironment with bone cells and immune cells present in the adjacent bone marrow. Osteoclasts, which degrade the bone matrix, express costimulatory molecules on their surface, like antigen-presenting cells, which enable them to interact with immune and cancer cells, exerting an immunosuppressive effect on the bone microenvironment. They also maintain a vicious circle with tumor cells by releasing growth factors during bone resorption. The aim of the project is to gain a better understanding of these interactions and lay the communication pathways involved between osteoclasts and cancer cells, via checkpoints molecules. This will enable us to understand the bone response when using checkpoint inhibitors (ICIs), which have revolutionized the management of certain cancers, but seem to have less effect on bone metastases. To better understand the local interactions of osteoclasts with the immune and neoplastic environment, and as reported for other immune checkpoint molecules such as CD80/86 or PDL-1, we studied ICOSL expression in human osteoclasts, and its impact on multinucleation and bone resorption, two phenotypic features of these cells. We were able to demonstrate ICOSL expression in our model of fetal monocyte-derived osteoclasts in long-term culture. Inhibition of ICOSL expression by DsiRNA resulted in a significant reduction in the number of multinucleated cells, and in bone resorption, compared with control DsiRNA. The impact of ICOSL on apoptosis is currently being evaluated. Finally, given the possibility of ICOSL binding to different receptors, including some that are characteristic of bone tissue, an evaluation of the ICOSL interactome under different conditions (depending on the matrix or type of ICOSL stimulation) has also been programmed. We have successfully completed the first stage of immunoprecipitation of ICOSL in mature osteoclasts. The samples will now be processed for mass spectrometry analysis. Our work underlines the importance of immune checkpoints in osteoclast activity and will help us to better understand the bone response to ICIs.","abstract_html":"When cancer cells metastasize to bone, they interact in the bone microenvironment with bone cells and immune cells present in the adjacent bone marrow. Osteoclasts, which degrade the bone matrix, express costimulatory molecules on their surface, like antigen-presenting cells, which enable them to interact with immune and cancer cells, exerting an immunosuppressive effect on the bone microenvironment. They also maintain a vicious circle with tumor cells by releasing growth factors during bone resorption. The aim of the project is to gain a better understanding of these interactions and lay the communication pathways involved between osteoclasts and cancer cells, via checkpoints molecules. This will enable us to understand the bone response when using checkpoint inhibitors (ICIs), which have revolutionized the management of certain cancers, but seem to have less effect on bone metastases. To better understand the local interactions of osteoclasts with the immune and neoplastic environment, and as reported for other immune checkpoint molecules such as CD80/86 or PDL-1, we studied ICOSL expression in human osteoclasts, and its impact on multinucleation and bone resorption, two phenotypic features of these cells. We were able to demonstrate ICOSL expression in our model of fetal monocyte-derived osteoclasts in long-term culture. Inhibition of ICOSL expression by DsiRNA resulted in a significant reduction in the number of multinucleated cells, and in bone resorption, compared with control DsiRNA. The impact of ICOSL on apoptosis is currently being evaluated. Finally, given the possibility of ICOSL binding to different receptors, including some that are characteristic of bone tissue, an evaluation of the ICOSL interactome under different conditions (depending on the matrix or type of ICOSL stimulation) has also been programmed. We have successfully completed the first stage of immunoprecipitation of ICOSL in mature osteoclasts. The samples will now be processed for mass spectrometry analysis. Our work underlines the importance of immune checkpoints in osteoclast activity and will help us to better understand the bone response to ICIs.","abstract_has_math":false,"creators":["Badiane, Papa Yaya"],"institution":"Université de Sherbrooke","degree_name":"M. Sc.","degree_level":"Maîtrise","degree_discipline":"Immunologie","degree_department":null,"school":null,"contributors":[],"advisors":["Roux, Sophie"],"committee_chairs":[],"committee_members":[],"year":2024,"date_issued":"2024","date_published":"2024","updated_at":"2026-07-27T21:07:32Z","subjects":["Ostéoclastes","Métastases osseuses","Système immunitaire","Point de contrôle","Osteoclast","Bone metastases","Immune system","Immune checkpoints"],"languages":["fr"],"rights":[],"rights_urls":["http://creativecommons.org/licenses/by-nc-nd/2.5/ca/"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11143/21815","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Roux, Sophie"]},{"key":"dc:creator","label":"Author","values":["Badiane, Papa Yaya"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-08-12T19:49:37Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-08-12T19:49:37Z"]},{"key":"dc:date.issued","label":"Date","values":["2024"]},{"key":"dc:publisher","label":"Institution","values":["Université de Sherbrooke"]},{"key":"dc:type","label":"Dc Type","values":["Mémoire de maîtrise"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Immunologie"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Maîtrise"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M. Sc."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Faculté de médecine et des sciences de la santé"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Ostéoclastes","Métastases osseuses","Système immunitaire","Point de contrôle","Osteoclast","Bone metastases","Immune system","Immune checkpoints"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["fr"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://creativecommons.org/licenses/by-nc-nd/2.5/ca/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/11143/21815"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["When cancer cells metastasize to bone, they interact in the bone microenvironment with bone cells and immune cells present in the adjacent bone marrow. Osteoclasts, which degrade the bone matrix, express costimulatory molecules on their surface, like antigen-presenting cells, which enable them to interact with immune and cancer cells, exerting an immunosuppressive effect on the bone microenvironment. They also maintain a vicious circle with tumor cells by releasing growth factors during bone resorption. The aim of the project is to gain a better understanding of these interactions and lay the communication pathways involved between osteoclasts and cancer cells, via checkpoints molecules. This will enable us to understand the bone response when using checkpoint inhibitors (ICIs), which have revolutionized the management of certain cancers, but seem to have less effect on bone metastases. To better understand the local interactions of osteoclasts with the immune and neoplastic environment, and as reported for other immune checkpoint molecules such as CD80/86 or PDL-1, we studied ICOSL expression in human osteoclasts, and its impact on multinucleation and bone resorption, two phenotypic features of these cells. We were able to demonstrate ICOSL expression in our model of fetal monocyte-derived osteoclasts in long-term culture. Inhibition of ICOSL expression by DsiRNA resulted in a significant reduction in the number of multinucleated cells, and in bone resorption, compared with control DsiRNA. The impact of ICOSL on apoptosis is currently being evaluated. Finally, given the possibility of ICOSL binding to different receptors, including some that are characteristic of bone tissue, an evaluation of the ICOSL interactome under different conditions (depending on the matrix or type of ICOSL stimulation) has also been programmed. We have successfully completed the first stage of immunoprecipitation of ICOSL in mature osteoclasts. The samples will now be processed for mass spectrometry analysis. Our work underlines the importance of immune checkpoints in osteoclast activity and will help us to better understand the bone response to ICIs.","Les cellules cancéreuses, lors de métastases osseuses, interagissent dans le microenvironnement osseux avec les cellules osseuses, dont les ostéoclastes, cellules dégradant la matrice osseuse et les cellules immunes présentes dans la moelle osseuse adjacente. Ces interactions impliquent des molécules de costimulation appelées point de contrôle immunitaire présent à la surface des ostéoclastes et des cellules présentatrices d’antigènes. Cela leur permet d’interagir avec les cellules immunes et cancéreuses, et exerce un effet immunosuppresseur sur le microenvironnement osseux. Les ostéoclastes entretiennent aussi un cercle vicieux de dégradation accrue de la matrice osseuse et de prolifération des cellules tumorales en libérant des facteurs de croissance lors de la résorption osseuse. Le but du projet est de mieux comprendre ces interactions et les voies de communication impliquées entre les ostéoclastes et les cellules cancéreuses, en particulier via les points de contrôle, ce qui permettrait d’appréhender la réponse osseuse lors de l’utilisation d’inhibiteurs de points de contrôle (ICIs), qui ont révolutionné la prise en charge de certains cancers, mais qui semblent moins agir sur les métastases osseuses. Pour mieux comprendre les interactions locales des ostéoclastes avec l’environnement immun et néoplasique, et comme cela a été rapporté pour d'autres molécules de point de contrôle immunitaire telles que CD80/86 ou PDL-1, nous avons étudié l’expression de ICOSL dans les ostéoclastes humains, et son impact sur la multinucléation et la résorption osseuse, deux caractéristiques phénotypiques de ces cellules. Nous avons ainsi été en mesure de démontrer l’expression de ICOSL dans notre modèle d’ostéoclastes dérivés de monocytes fœtaux en culture à long terme. L’inhibition de l’expression de ICOSL par DsiRNA a entraîné une réduction importante du nombre de cellules multinucléées, et de la résorption osseuse par rapport à un DsiRNA contrôle. L’impact de ICOSL sur l’apoptose est en cours d’évaluation. Enfin, compte tenu de la possibilité de liaison de ICOSL à différents récepteurs, dont certaines caractéristiques du tissu osseux, une évaluation de l’interactome de ICOSL dans différentes conditions (selon la matrice ou le type de stimulation de ICOSL) a également été programmée. Nous avons réalisé avec succès la première étape d’immunoprécipitation de ICOSL dans les ostéoclastes matures. Les échantillons pourront ensuite être traités pour une analyse par spectrométrie de masse. Nos travaux soulignent l’importance des points de contrôles immuns dans l’activité des ostéoclastes, et permettront de mieux comprendre la réponse osseuse des ICIs."]},{"key":"dc:title","label":"Title","values":["Étude de l’expression et du rôle du ligand du co-stimulateur inductible des cellules T (ICOSL) dans les ostéoclastes humains"]}]}],"canonical_facts":{"dc:contributor.advisor":["Roux, Sophie"],"dc:creator":["Badiane, Papa Yaya"],"dc:date.accessioned":["2024-08-12T19:49:37Z"],"dc:date.available":["2024-08-12T19:49:37Z"],"dc:date.issued":["2024"],"dc:description.abstract":["When cancer cells metastasize to bone, they interact in the bone microenvironment with bone cells and immune cells present in the adjacent bone marrow. Osteoclasts, which degrade the bone matrix, express costimulatory molecules on their surface, like antigen-presenting cells, which enable them to interact with immune and cancer cells, exerting an immunosuppressive effect on the bone microenvironment. They also maintain a vicious circle with tumor cells by releasing growth factors during bone resorption. The aim of the project is to gain a better understanding of these interactions and lay the communication pathways involved between osteoclasts and cancer cells, via checkpoints molecules. This will enable us to understand the bone response when using checkpoint inhibitors (ICIs), which have revolutionized the management of certain cancers, but seem to have less effect on bone metastases. To better understand the local interactions of osteoclasts with the immune and neoplastic environment, and as reported for other immune checkpoint molecules such as CD80/86 or PDL-1, we studied ICOSL expression in human osteoclasts, and its impact on multinucleation and bone resorption, two phenotypic features of these cells. We were able to demonstrate ICOSL expression in our model of fetal monocyte-derived osteoclasts in long-term culture. Inhibition of ICOSL expression by DsiRNA resulted in a significant reduction in the number of multinucleated cells, and in bone resorption, compared with control DsiRNA. The impact of ICOSL on apoptosis is currently being evaluated. Finally, given the possibility of ICOSL binding to different receptors, including some that are characteristic of bone tissue, an evaluation of the ICOSL interactome under different conditions (depending on the matrix or type of ICOSL stimulation) has also been programmed. We have successfully completed the first stage of immunoprecipitation of ICOSL in mature osteoclasts. The samples will now be processed for mass spectrometry analysis. Our work underlines the importance of immune checkpoints in osteoclast activity and will help us to better understand the bone response to ICIs.","Les cellules cancéreuses, lors de métastases osseuses, interagissent dans le microenvironnement osseux avec les cellules osseuses, dont les ostéoclastes, cellules dégradant la matrice osseuse et les cellules immunes présentes dans la moelle osseuse adjacente. Ces interactions impliquent des molécules de costimulation appelées point de contrôle immunitaire présent à la surface des ostéoclastes et des cellules présentatrices d’antigènes. Cela leur permet d’interagir avec les cellules immunes et cancéreuses, et exerce un effet immunosuppresseur sur le microenvironnement osseux. Les ostéoclastes entretiennent aussi un cercle vicieux de dégradation accrue de la matrice osseuse et de prolifération des cellules tumorales en libérant des facteurs de croissance lors de la résorption osseuse. Le but du projet est de mieux comprendre ces interactions et les voies de communication impliquées entre les ostéoclastes et les cellules cancéreuses, en particulier via les points de contrôle, ce qui permettrait d’appréhender la réponse osseuse lors de l’utilisation d’inhibiteurs de points de contrôle (ICIs), qui ont révolutionné la prise en charge de certains cancers, mais qui semblent moins agir sur les métastases osseuses. Pour mieux comprendre les interactions locales des ostéoclastes avec l’environnement immun et néoplasique, et comme cela a été rapporté pour d'autres molécules de point de contrôle immunitaire telles que CD80/86 ou PDL-1, nous avons étudié l’expression de ICOSL dans les ostéoclastes humains, et son impact sur la multinucléation et la résorption osseuse, deux caractéristiques phénotypiques de ces cellules. Nous avons ainsi été en mesure de démontrer l’expression de ICOSL dans notre modèle d’ostéoclastes dérivés de monocytes fœtaux en culture à long terme. L’inhibition de l’expression de ICOSL par DsiRNA a entraîné une réduction importante du nombre de cellules multinucléées, et de la résorption osseuse par rapport à un DsiRNA contrôle. L’impact de ICOSL sur l’apoptose est en cours d’évaluation. Enfin, compte tenu de la possibilité de liaison de ICOSL à différents récepteurs, dont certaines caractéristiques du tissu osseux, une évaluation de l’interactome de ICOSL dans différentes conditions (selon la matrice ou le type de stimulation de ICOSL) a également été programmée. Nous avons réalisé avec succès la première étape d’immunoprécipitation de ICOSL dans les ostéoclastes matures. Les échantillons pourront ensuite être traités pour une analyse par spectrométrie de masse. Nos travaux soulignent l’importance des points de contrôles immuns dans l’activité des ostéoclastes, et permettront de mieux comprendre la réponse osseuse des ICIs."],"dc:identifier.uri":["http://hdl.handle.net/11143/21815"],"dc:language.iso":["fr"],"dc:publisher":["Université de Sherbrooke"],"dc:rights.uri":["http://creativecommons.org/licenses/by-nc-nd/2.5/ca/"],"dc:subject":["Ostéoclastes","Métastases osseuses","Système immunitaire","Point de contrôle","Osteoclast","Bone metastases","Immune system","Immune checkpoints"],"dc:title":["Étude de l’expression et du rôle du ligand du co-stimulateur inductible des cellules T (ICOSL) dans les ostéoclastes humains"],"dc:type":["Mémoire de maîtrise"],"thesis:degree_discipline":["Immunologie"],"thesis:degree_level":["Maîtrise"],"thesis:degree_name":["M. Sc."],"thesis:institution_name":["Faculté de médecine et des sciences de la santé"]},"updated_at":"2026-07-27T21:07:32Z"}