One of the characteristics of prognostically infaust uveal melanoma (UM) is an inflammatory phenotype, which is characterized by high numbers of infiltrating T cells and macrophages, and a high HLA Class I expression. We wondered how this inflammation is regulated, and considered that one of the most important regulators of inflammation, the NFkB pathway, might play a role. We analyzed 64 UM samples for expression of HLA Class I, its regulators, and of members of the NFkB transcription family, using an Illumina HT12V4 array. HLA Class I expression and infiltrating immune cells were also determined by immunohistochemical staining. Information was obtained regarding chromosome status by Affymetrix Nsp array. Our analysis shows that expression of NFkB1, NFkB2 and RELB positively correlates with the level of HLA Class I expression and the number of infiltrating T cells and macrophages, while SPP1 and PPARγ are negatively correlated. Increased levels of NFkB1 and NFkB2 and decreased levels of SPP1 and PPARγ are seen in Monosomy 3/BAP1-negative tumors. This is also the case in non-inflammatory UM, indicating that our observation not only involves infiltrating leukocytes but the tumor cells themselves. We report that the NFkB pathway is associated with inflammation and HLA Class I expression in UM, and is upregulated when BAP1 expression is lost.

Inflammation, characterized by high numbers of infiltrating leukocytes and a high HLA Class I expression, is associated with a bad prognosis in uveal melanoma (UM). We wondered whether mutations in GNA11 or GNAQ differentially affect inflammation and HLA expression, and thereby progression of the disease. We analyzed data of 59 primarily enucleated UM eyes. The type of GNAQ/11 mutation was analyzed using dPCR; chromosome aberrations were determined by Fluorescence in Situ Hybridization (FISH), karyotyping, and single nucleotide polymorphism (SNP) analysis, and mRNA expression by Illumina PCR. Comparing tumors with a GNAQ mutation with those with a GNA11 mutation yielded no significant differences in histopathological characteristics, infiltrate, or HLA expression. When comparing the Q209L mutations with Q209P mutations in tumors with monosomy of chromosome 3, a higher mitotic count was found in the Q209P/M3 tumors (p = 0.007). The Kaplan-Meier (KM) curves between the patients of the different groups were not significantly different. We conclude that the type (Q209P/Q209L) or location of the mutation (GNA11/GNAQ) do not have a significant effect on the immunological characteristics of the tumors, such as infiltrate and HLA Class I expression. Chromosome 3 status was the main determinant in explaining the difference in infiltrate and HLA expression.