Regulation of inflammation in uveal melanoma

Abstract

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 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.