Cancers, Vol. 13, Pages 4445: LAG3 and Its Ligands Show Increased Expression in High-Risk Uveal Melanoma

Cancers, Vol. 13, Pages 4445: LAG3 and Its Ligands Show Increased Expression in High-Risk Uveal Melanoma Cancers doi: 10.3390/cancers13174445 Authors: Zahra Souri Annemijn P. A. Wierenga Wilma G. M. Kroes Pieter A. van der Velden Robert M. Verdijk Michael Eikmans Gregorius P. M. Luyten Martine J. Jager Uveal melanoma (UM) is a rare ocular malignancy which originates in the uveal tract, and often gives rise to metastases. Potential targets for immune checkpoint inhibition are lymphocyte-activation gene 3 (LAG3) and its ligands. We set out to analyse the distribution of these molecules in UM. The expression of mRNA was determined using an Illumina array in 64 primary UM from Leiden. The T lymphocyte fraction was determined by digital droplet PCR. In a second cohort of 15 cases from Leiden, mRNA expression was studied by Fluidigm qPCR, while a third cohort consisted of 80 UM from TCGA. In the first Leiden cohort, LAG3 expression was associated with the presence of epithelioid cells (p = 0.002), monosomy of chromosome 3 (p = 0.004), and loss of BAP1 staining (p = 0.001). In this Leiden cohort as well as in the TCGA cohort, LAG3 expression correlated positively with the expression of its ligands: LSECtin, Galectin-3, and the HLA class II molecules HLA-DR, HLA-DQ, and HLA-DP (all p < 0.001). Furthermore, ligands Galectin-3 and HLA class II were increased in monosomy 3 tumours and the expression of LAG3 correlated with the presence of an inflammatory...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research