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

Vincenza Maria Elena Bonfiglio, Santa Mammana, Ferdinando Nicoletti, Andrea Russo, Matteo Fallico, Matteo Fallico, Vincenza Bonfiglio, Michele Reibaldi, Rosario Caltabiano, Teresio Avitabile, Emanuela Mazzon, Maria Sofia Basile, Paolo Fagone, Antonio Longo, Andrea Russo, Gabriella Mazzon

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)e0210276-
Number of pages16
JournalPLoS One
Volume14
Publication statusPublished - 2019

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General

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