Leiden University Scholarly Publications

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Souri, Z. (2021)

Regulation of inflammation in uveal melanoma

Doctoral Thesis
As HLA Class I expression is an important target for cytotoxic T cells but an in inhibitor of NK
cells, we were interested in the regulation of its expression.
We review HLA expression in UM, how it is involved in the inflammatory phenotype, how it is regulated and how putative treatments might be effective in its expression.
We investigate the potential role of the NFkB pathway in the regulation of inflammation in UM and its potential association with HLA Class I expression.
In order to increase our understanding for the reason behind the elevated HLA Class I expression in UM tumours, we investigate the involvement of epigenetics. We focus on a set of epigenetic enzymes called histone deacetylases and report that these regulators are highly expressed in Monosomy 3 UM.
We wonder whether HDAC expression is influenced by the presence of infiltrating lymphocytes and macrophages.
We focus on miRNA’s as another set of epigenetic regulators of inflammation. We...Show moreAs HLA Class I expression is an important target for cytotoxic T cells but an in inhibitor of NK
cells, we were interested in the regulation of its expression.
We review HLA expression in UM, how it is involved in the inflammatory phenotype, how it is regulated and how putative treatments might be effective in its expression.
We investigate the potential role of the NFkB pathway in the regulation of inflammation in UM and its potential association with HLA Class I expression.
In order to increase our understanding for the reason behind the elevated HLA Class I expression in UM tumours, we investigate the involvement of epigenetics. We focus on a set of epigenetic enzymes called histone deacetylases and report that these regulators are highly expressed in Monosomy 3 UM.
We wonder whether HDAC expression is influenced by the presence of infiltrating lymphocytes and macrophages.
We focus on miRNA’s as another set of epigenetic regulators of inflammation. We investigate the potential relation of a set of 125 miRNA’s with HLA Class I expression and the presence of an infiltrate in UM and report two patterns of miRNA expression.
We study the LAG3 immune checkpoint in UM tumours. As immune checkpoints might be responsible for the T cell exhaustion which is observed in UM, we investigate the involvement of LAG in prognostication and study how LAG3 and its ligands are distributed among different UM tumours.
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Cancer
Uveal melanoma
Inflammation
HLA, Immunotherapy
Chromosome 3
BAP1
All authors
Souri, Z.
Supervisor
Jager, M.J.
Co-supervisor
Jochemsen, A.G.
Committee
Luyten, G.P.M.; Elas, M.; Esmaeli, B.; Kilic, E.; Pakdel, F.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2021-09-14
ISBN (print)
9789464233421

Funding

Sponsorship
This thesis was made possible by the contribution of the Iranian Ministry of Science Research and Technology; Grant UL 2011-4991 from the Dutch Cancer Society (KW F); Stichting Leids Oogheelkundig Ondersteunings Fonds LOOF; a Horizon 2020 grant from the European Community; CURE UM, nr. 667787; Nelly Reef Fund and Ms I. Brouwer