PhD defence
Improving immunotherapy for melanoma: models, biomarkers and regulatory T cells
- D Rao
- Date
- Tuesday 12 December 2023
- Time
- Location
-
Academy Building
Rapenburg 73
2311 GJ Leiden
Supervisor(s)
- Prod.dr. C.U. Blank
- Prof.dr. D.S. Peeper (NKI)
Summary
While immune checkpoint blockade (CTLA-4/ PD-1) therapy has resulted in durable responses in most patients with advanced stage cutaneous melanoma, some patients do not benefit from currently available immunotherapies, due to several resistance mechanisms. The work described in this thesis aims to improve responses of a subset of melanoma patients to immunotherapy. Firstly, mouse melanoma tumor models are developed that closely resemble some of the resistance mechanisms occurring in patient tumors. These models are useful for research aiming to understand and tackle resistance mechanisms to immunotherapy. Thereafter, a prognostic biomarker is used to identify the subset of patients that are unlikely to benefit from CTLA-4 and/ or PD-1 blockade therapy. It is then evaluated whether this subset of patients would benefit from additional combination approaches. Despite encouraging pre-clinical results showing enhanced anti-tumor immune responses by combining histone deacetylase inhibitors with CTLA-4 + PD-1 blockade, this combination did not result in improved responses in patients with stage III melanoma in the clinic. The later part of this thesis focuses on an immune cell subset, namely regulatory T cells, which are known to suppress anti-tumor immune responses. Thus, their presence in the tumor microenvironment is detrimental to tumor cell killing. This thesis provides an increased understanding of the metabolic adaptation of regulatory T cells to conditions in the tumor microenvironment and propose that targeting these adaptations might likely overcome the suppression by regulatory T cells and enhance responses to immunotherapy.
PhD dissertations
Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.
Press enquiries (journalists only)
General information
Beadle's Office
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