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

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

Research output: Contribution to journalArticle

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
Article numbere0210276
JournalPLoS One
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 2019

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Differential modulation and prognostic values of immune-escape genes in uveal melanoma'. Together they form a unique fingerprint.

  • Cite this

    Basile, M. S., Mazzon, E., Russo, A., Mammana, S., Longo, A., Bonfiglio, V., Fallico, M., Caltabiano, R., Fagone, P., Nicoletti, F., Avitabile, T., & Reibaldi, M. (2019). Differential modulation and prognostic values of immune-escape genes in uveal melanoma. PLoS One, 14(1), [e0210276]. https://doi.org/10.1371/journal.pone.0210276