A novel Treg subset involved in melanoma immune evasion

• Lymphocytes are particularly rich in FKBP51 (FKBP5gene), an immunophilin better known as the intracellular receptor for FK506 and rapamycin. Melanoma/immune-cell interaction, through PD-L1/PD1, generates FKBP5 splicing, producing a lower molecular weight FKBP51 form, termed FKBP51s. • Tregs is a heterogeneous population with respect to their immunosuppressive capability, which is usually increased in melanoma patients. FKBP51s is associated with a highly metabolically active profile of Tregs with strong suppressive capability. • Melanoma patients that benefit from immune-checkpoint targeted therapy are recognizable by an expansion of FKBP51s+Treg subset which may be involved in de-activation of stimulatory co-signalling pathways, in support of tumor immune evasion