Casado, Anna (2026) Multiple Immune Checkpoint Blockade in classic Hodgkin Lymphoma. Master's Research Project 1, Biomedical Sciences.
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Abstract
Immune checkpoint blockade (ICB) has become a promising therapeutic approach for classic Hodgkin lymphoma (cHL), targeting immune checkpoints (IC) or inhibitory receptors and ligands expressed in its abundant anti-inflammatory tumor microenvironment (TME) cells, of which functionally exhausted T cells represent a large fraction. However, despite overall responses to PD-1 targeted ICB being good (65–87%), complete responses remain considerably low (17-25%). These responses highlight that other immune checkpoints or axes may be involved in the exhaustion process. The phenotype is characterised by the expression of multiple immune IC molecules including TIGIT, OX40, TIM-3, LAG-3, BTLA, CTLA-4 along with PD-1 as reported in existing literature, but the knowledge on the magnitude of their contribution to the exhausted phenotype or the observed resistance to ICB remains limited . Using a short-term cHL in vitro model, this project aims to explore and determine the effect of the different IC molecules on T cell function in cHL. Additionally, determine ICB combinations that could potentially increase ICB efficacy. In the co-culture model healthy donor pheripheral blood mononuclear cells (PBMCs) are co-cultured with irradiated cHL cell lines L428 and SUP-HD1 in two steps: First, IC expression levels are measured using flow cytometry upon activation. Then, their effect on the exhastion phenotype is measured using inhibitors and IFN-γ and IL-2 ELISAs. The model showed limited results. The most promising ones where when co-cultured with only anti-CD3. Under this conditions, PD-1, TIM-3 and CTLA-4 showed the highest contribution to T cell exhaustion. Thus, combining TIM-3 and CTLA-4 inhibition could increase ICB efficacy.
| Item Type: | Thesis (Master's Research Project 1) |
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| Supervisor name: | Diepstra, A. and Visser, A. |
| Degree programme: | Biomedical Sciences |
| Thesis type: | Master's Research Project 1 |
| Language: | English |
| Date Deposited: | 28 Jul 2026 06:58 |
| Last Modified: | 28 Jul 2026 06:58 |
| URI: | https://fse.studenttheses.ub.rug.nl/id/eprint/37470 |
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