Differential modulation and prognostic values of immune-escape genes in uveal melanoma

PLoS One. 2019 Jan 17;14(1):e0210276. doi: 10.1371/journal.pone.0210276. eCollection 2019.

Abstract

Uveal melanoma (UM) is the most common primary intraocular cancer in adults. In the present study, we aimed to characterize the immunological features of primary UM cancer and to provide an association with prognostic markers and outcome. Also, we assessed the influence of the microenvironment on the expression of inhibitory immune checkpoints in UM. Genes of interest included MHC Class I and Class II molecules, as well as inhibitory immune-checkpoints, i.e. PDL1, PDL2, B7-H3, B7-H4, TBFRSF6B, CD47, CD155, GAL9, HVEM and CD200. We observed significant lower levels of MHC genes in UM cells as compared to normal uveal melanocytes. Unexpectedly however, the expression levels of most of the analyzed inhibitory immune-checkpoint genes were not different in cancer cells as compared to normal melanocytes, with the exception of CD200 and HVEM, that resulted significantly reduced. On the other hand, PDL1 inversely correlated with OS, PFS and thickness of the tumor. Also, PDL1, along with PDL2, expression significantly increased under inflammatory conditions. Finally, for the first time, we propose a possible role for CD47 in the immune evasive properties of UM. We show here that CD47 is significantly upregulated by UM cells following inflammatory stimuli and that it represents a good independent predictor of disease progression. The results from this study may propel advances in the development of immune-based therapies for UM patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism*
  • Humans
  • Inflammation / physiopathology*
  • Melanocytes / cytology
  • Melanocytes / immunology*
  • Melanocytes / metabolism
  • Melanoma / immunology*
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Prognosis
  • Uveal Neoplasms / immunology*
  • Uveal Neoplasms / metabolism
  • Uveal Neoplasms / pathology*

Substances

  • Biomarkers

Supplementary concepts

  • Uveal melanoma

Grants and funding

This study was supported by current research funds 2016 of IRCCS "Centro Neurolesi "Bonino Pulejo", Messina-Italy.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.