Immunomodulatory pathways regulate expression of a spliced FKBP51 isoform in lymphocytes of melanoma patients

Simona Romano, Anna D'Angelillo, Stefania Staibano, Ester Simeone, Paolo D'Arrigo, Paolo Antonio Ascierto, Massimiliano Scalvenzi, Massimo Mascolo, Gennaro Ilardi, Francesco Merolla, Egle Jovarauskaite, Maria Fiammetta Romano

Research output: Contribution to journalArticle

Abstract

FKBP51 (gene FKBP5) is an immunophilin capable of immunosuppression expressed in melanoma and lymphocytes. We found increased levels of a spliced FKBP5 variant in the PBMCs of 124 patients with melanoma. This variant encodes for an unknown isoform (FKBP51s). We hypothesized that FKBP51s resulted from tumour interaction with immune cells, through PDL-1/PD-1. To address this issue, we performed melanoma/PBMC cocultures. Furthermore, the immunohistochemistry of 76 melanoma specimens served to investigate whether FKBP51s stained tumour infiltrating lymphocytes. Our results showed that PBMCs expressed FKBP51s when cocultured with melanoma. Tumour PDL-1 knockdown or anti-PD-1 reduced FKBP51s expression in cocultured PBMCs. IHC showed a strong FKBP51s signal in tumour infiltrating lymphocytes, and lymphocytes of the invasion front of the tumour, along with melanoma PDL-1 expression. When overexpressed in melanoma, FKBP51s facilitated PDL-1 expression on the cell surface. In conclusion, our study shows that FKBP51s marks the PBMCs of patients with melanoma and is exploited by the tumour to immunomodulate through PDL-1.

Original languageEnglish
Pages (from-to)442-452
Number of pages11
JournalPigment Cell and Melanoma Research
Volume28
Issue number4
DOIs
Publication statusPublished - Jul 1 2015

Keywords

  • FKBP51 spliced isoform
  • Immune signature
  • Lymphocytes
  • Melanoma
  • PDL-1

ASJC Scopus subject areas

  • Dermatology
  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Romano, S., D'Angelillo, A., Staibano, S., Simeone, E., D'Arrigo, P., Ascierto, P. A., Scalvenzi, M., Mascolo, M., Ilardi, G., Merolla, F., Jovarauskaite, E., & Romano, M. F. (2015). Immunomodulatory pathways regulate expression of a spliced FKBP51 isoform in lymphocytes of melanoma patients. Pigment Cell and Melanoma Research, 28(4), 442-452. https://doi.org/10.1111/pcmr.12378