Recently, our group demonstrated that the inhibitory immune checkpoint PD-L1/PD1 promoted the alternative splicing of FKBP5 gene, resulting in increased expression of its variant 4, in PBMC of melanoma patients. Such variant 4 is translated into a truncated protein, termed FKBP51s. Based on the relevant role for co-inhibitory signaling in tumor immune escape, we thought to measure the expression of such a molecular sensor of PD-L1/PD1 interaction in melanoma patients, by PBMC immunophenotyping. The study was conducted on a cohort of 118 patients and 77 age- and sex-matched healthy controls. Blood samples were collected before patients underwent ipilimumab treatment. In 64 out of 118 patients, expression of FKBP51s was also assessed in regulatory T cells. Our findings showed that, physiologically, each PBMC subset analyzed contained an FKBP51spos fraction, which resulted expanded in melanoma patients. CD4 T lymphocytes showed the FKBP51sneg subset significantly impaired. Treg count was increased, in accordance with previous studies. The study of FKBP51sposTregs allowed to identify a subgroup of nonresponder patients to ipilimumab (p=0.002). In conclusion, FKBP51s-based immunophenotype of melanoma patients revealed several profiles virtually related to a negative immune regulatory control and disclosed an unknown Treg subset potentially useful in the selection of patients candidate to immunotherapy.
An immunophenotype approach identified an unknown Treg subset in PBMC of melanoma patients, as associated with response to anti-CTLA4 / Romano, MARIA FIAMMETTA. - (2017).
An immunophenotype approach identified an unknown Treg subset in PBMC of melanoma patients, as associated with response to anti-CTLA4
ROMANO, MARIA FIAMMETTA
2017
Abstract
Recently, our group demonstrated that the inhibitory immune checkpoint PD-L1/PD1 promoted the alternative splicing of FKBP5 gene, resulting in increased expression of its variant 4, in PBMC of melanoma patients. Such variant 4 is translated into a truncated protein, termed FKBP51s. Based on the relevant role for co-inhibitory signaling in tumor immune escape, we thought to measure the expression of such a molecular sensor of PD-L1/PD1 interaction in melanoma patients, by PBMC immunophenotyping. The study was conducted on a cohort of 118 patients and 77 age- and sex-matched healthy controls. Blood samples were collected before patients underwent ipilimumab treatment. In 64 out of 118 patients, expression of FKBP51s was also assessed in regulatory T cells. Our findings showed that, physiologically, each PBMC subset analyzed contained an FKBP51spos fraction, which resulted expanded in melanoma patients. CD4 T lymphocytes showed the FKBP51sneg subset significantly impaired. Treg count was increased, in accordance with previous studies. The study of FKBP51sposTregs allowed to identify a subgroup of nonresponder patients to ipilimumab (p=0.002). In conclusion, FKBP51s-based immunophenotype of melanoma patients revealed several profiles virtually related to a negative immune regulatory control and disclosed an unknown Treg subset potentially useful in the selection of patients candidate to immunotherapy.File | Dimensione | Formato | |
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Descrizione: programma seminari DMMBM/IEOS gennaio/febbraio 2017
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