BACKGROUND: Programmed death-1 (PD-1) is a marker for human neoplastic T cells. Here, we evaluated whether or not PD-1 was also a marker for human mastocytosis, and explored the role of PD-1 in human mastocytosis cells. METHODS: Immunohistochemical analysis was used to evaluate the expression of PD-1 in clinical samples of human cutaneous mastocytosis. The expression of PD-1 in human mastocytosis cell lines was checked by RT-PCR, western blotting and flow cytometry. We stimulated human mastocytosis cell lines (LAD2 and HMC1.2) with recombinant ligand for PD-1, PD-L1 (rPD-L1), and tested the proliferative activity and the status of signal molecules by Cell Counting Kit-8 and ELISA, respectively. RESULTS: Ten of 30 human cutaneous mastocytosis cases (33.3%) expressed PD-1 protein. We also found that a human mastocytosis line LAD2 cells expressed PD-1 protein on their surfaces. The administration with rPD-L1 suppressed the stem cell factor-dependent growth of the LAD2 cells. And, rPD-L1 activated SHP-1 and SHP-2 simultaneously, and decreased the phosphorylation of AKT, in LAD2 cells. In contrast, we could not detect the expression of PD-1, and the significant effect of rPD-L1 on the mutated KIT-driven growth of HMC1.2 cells. CONCLUSIONS: PD-1 could be a marker for human cutaneous mastocytosis and regulate the growth of human PD-1-positive mastocytosis cells.
BACKGROUND:Programmed death-1 (PD-1) is a marker for human neoplastic T cells. Here, we evaluated whether or not PD-1 was also a marker for humanmastocytosis, and explored the role of PD-1 in humanmastocytosis cells. METHODS: Immunohistochemical analysis was used to evaluate the expression of PD-1 in clinical samples of humancutaneous mastocytosis. The expression of PD-1 in humanmastocytosis cell lines was checked by RT-PCR, western blotting and flow cytometry. We stimulated humanmastocytosis cell lines (LAD2 and HMC1.2) with recombinant ligand for PD-1, PD-L1 (rPD-L1), and tested the proliferative activity and the status of signal molecules by Cell Counting Kit-8 and ELISA, respectively. RESULTS: Ten of 30 humancutaneous mastocytosis cases (33.3%) expressed PD-1 protein. We also found that a humanmastocytosis line LAD2 cells expressed PD-1 protein on their surfaces. The administration with rPD-L1 suppressed the stem cell factor-dependent growth of the LAD2 cells. And, rPD-L1 activated SHP-1 and SHP-2 simultaneously, and decreased the phosphorylation of AKT, in LAD2 cells. In contrast, we could not detect the expression of PD-1, and the significant effect of rPD-L1 on the mutated KIT-driven growth of HMC1.2 cells. CONCLUSIONS:PD-1 could be a marker for humancutaneous mastocytosis and regulate the growth of humanPD-1-positive mastocytosis cells.
Authors: Ellen W Hatch; Mary Beth Geeze; Cheyenne Martin; Mohamed E Salama; Karin Hartmann; Gregor Eisenwort; Katharina Blatt; Peter Valent; Jason Gotlib; Ji-Hyun Lee; Lu Chen; Heather H Ward; Diane S Lidke; Tracy I George Journal: Blood Adv Date: 2018-02-13