Details

Autor(en) / Beteiligte

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

Titel

Immunomodulatory pathways regulate expression of a spliced FKBP 51 isoform in lymphocytes of melanoma patients

Ist Teil von

• Pigment cell and melanoma research, 2015-07, Vol.28 (4), p.442-452

Erscheinungsjahr

2015

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Summary FKBP 51 (gene FKBP 5) is an immunophilin capable of immunosuppression expressed in melanoma and lymphocytes. We found increased levels of a spliced FKBP 5 variant in the PBMC s of 124 patients with melanoma. This variant encodes for an unknown isoform ( FKBP 51s). We hypothesized that FKBP 51s 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 FKBP 51s stained tumour infiltrating lymphocytes. Our results showed that PBMC s expressed FKBP 51s when cocultured with melanoma. Tumour PDL ‐1 knockdown or anti‐ PD ‐1 reduced FKBP 51s expression in cocultured PBMC s. IHC showed a strong FKBP 51s signal in tumour infiltrating lymphocytes, and lymphocytes of the invasion front of the tumour, along with melanoma PDL ‐1 expression. When overexpressed in melanoma, FKBP 51s facilitated PDL ‐1 expression on the cell surface. In conclusion, our study shows that FKBP 51s marks the PBMC s of patients with melanoma and is exploited by the tumour to immunomodulate through PDL ‐1.