Soluble HLA in the Aqueous Humour of Uveal Melanoma Is Associated with Unfavourable Tumour Characteristics.

Annemijn P A Wierenga,Mieke Versluis,Niels J Brouwer,Robert M Verdijk,Sjoerd G Van Duinen,Marijke Spruyt-Gerritse,Michael Eikmans,Marina Marinkovic,Gülçin Gezgin,Gregorius P M Luyten,Martine J Jager,Els Van Beelen

doi:10.3390/cancers11081202

Annemijn P A Wierenga, Mieke Versluis + Show 10 more

Open Access

https://doi.org/10.3390/cancers11081202

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Journal: Cancers	Publication Date: Aug 18, 2019
Citations: 16	License type: CC BY 4.0

Affiliation: Leiden University Medical Center, Erasmus MC

Abstract

A high HLA expression in uveal melanoma (UM) is part of the prognostically unfavorable inflammatory phenotype. We wondered whether the presence of soluble HLA (sHLA) in the aqueous humour is associated with clinical, histopathological or genetic tumour characteristics, and represents tumour HLA expression and intratumoural inflammation. Aqueous humour from 108 UM patients was analysed for the presence of sHLA, using a Luminex assay specific for HLA Class I. Clinical and genetic parameters were compared between sHLA-positive and negative eyes. A qPCR analysis was performed on tumour tissue using a Fluidigm assay. In 19/108 UM-containing eyes, the sHLA level in the aqueous was above the detection limit. Tumours in sHLA-positive eyes were significantly larger, more frequently involved the ciliary body, and more often showed monosomy 3, gain of chromosome 8q and loss of BAP1 staining. Melanoma-related survival was worse in patients with sHLA-positive aqueous humour. sHLA in the aqueous did not represent the tumour’s HLA expression and did not relate to immune cell infiltration in the tumour. We conclude that UM-containing eyes may contain sHLA in the aqueous humour, where it is a prognostically-unfavourable sign and may influence local immune responses.

Highlights

Rare, with an incidence varying between 5.0 per million in the United States of America to 9.5 per million in Northern Europe, uveal melanoma (UM) is the most common primary ocular malignancy in adults [1,2]
We wondered whether analysis of soluble HLA (sHLA) molecules in aqueous humour can be used to indirectly determine HLA expression as an indicator of the presence of an inflammatory phenotype in the tumour, and whether sHLA expression in the aqueous humour is higher in eyes with a high-risk
Tumours from the sHLA-positive group belonged to higher American Joint Committee on Cancer (AJCC) stages (p < 0.001)

Summary

Introduction

With an incidence varying between 5.0 per million in the United States of America to 9.5 per million in Northern Europe, uveal melanoma (UM) is the most common primary ocular malignancy in adults [1,2]. The metastatic route of UM is mainly hematogenous, with about 50% of UM patients developing metastases, which occur predominantly in the liver [3,4]. Important genetic prognostic parameters are the monosomy of chromosome 3 (M3), a gain of the long arm of chromosome. Prognostically-infaust tumours often carry an inflammatory phenotype, which is characterised by infiltrating lymphocytes and macrophages and a high expression of HLA Class I [11,12,13]. Cancers 2019, 11, 1202 between a high HLA Class I expression in UM and an increased risk of developing metastases has been reported [11,12,14,15,16,17,18]. HLA expression is an important prerequisite for T cell-mediated immunotherapy, and information on a tumour’s HLA expression may help to identify cases that are good candidates for T cell-mediated therapy; for example, with IMCgp100

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