Retinoic acid elicits cytostatic, cytotoxic and immunomodulatory effects on uveal melanoma cells

Simona Vertuani, Eugenia Dubrovska, Victor Levitsky, Martine J. Jager, Rolf Kiessling, Jelena Levitskaya

Research output: Contribution to journalArticle

Abstract

The current therapy of uveal melanoma (UM) metastases remains inefficient, which warrants the development of new treatment modalities. For the first time we investigated the effects of retinoic acid (RA) on a panel of UM cell lines and found that RA induces morphological changes compatible with differentiation, suppresses proliferation and causes apoptosis in these cells. RA treatment resulted in an increase of p21, p27 and p53 protein levels and G1 arrest in UM cells, which correlated with significant down-modulation of surface Her2/neu proto-oncogene expression. In addition, RA-treated UM cells exhibited increased sensitivity to both MHC class I-restricted killing by cytotoxic T lymphocytes and NK cell-mediated lysis that were accompanied by more efficient conjugate formation between UM cells and killer lymphocytes. Taken together, our results implicate UM as a new target for treatment with retinoids and suggest that retinoids and T- or NK-cell based immunotherapy can have mutually enhancing effects in UM patients.

Original languageEnglish (US)
Pages (from-to)193-204
Number of pages12
JournalCancer Immunology Immunotherapy
Volume56
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

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Keywords

  • Cell death
  • Cytotoxic T lymphocytes
  • Retinoic acid
  • Uveal melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

Vertuani, S., Dubrovska, E., Levitsky, V., Jager, M. J., Kiessling, R., & Levitskaya, J. (2007). Retinoic acid elicits cytostatic, cytotoxic and immunomodulatory effects on uveal melanoma cells. Cancer Immunology Immunotherapy, 56(2), 193-204. https://doi.org/10.1007/s00262-006-0185-z