Étude de l’expression et du rôle du ligand du co-stimulateur inductible des cellules T (ICOSL) dans les ostéoclastes humains

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.

Name thesis:degree_name

M. Sc.

Level thesis:degree_level

Maîtrise

Discipline thesis:degree_discipline

Immunologie

Grantor dc:publisher

Université de Sherbrooke

Year dc:date.issued

2024

Author dc:creator

• Badiane, Papa Yaya

Advisor dc:contributor.advisor

• Roux, Sophie

• Ostéoclastes
• Métastases osseuses
• Système immunitaire
• Point de contrôle
• Osteoclast
• Bone metastases
• Immune system
• Immune checkpoints

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/2.5/ca/

Language dc:language.iso

fr

Handle dc:identifier.uri

http://hdl.handle.net/11143/21815

OAI identifier oai:identifier

oai:usherbrooke.scholaris.ca:11143/21815