Objectives: To investigate the expression profile of programmed death-1 (PD-1) on T cells derived from patients with cutaneous T-cell lymphoma (CTCL), analyze a potential mechanism responsible for upregulation of PD-1, and assess the correlation between blockade of its signaling pathway and improvement in immunological function.
Design: Translation research study.
Setting: University medical center.
Participants: Patients with Sézary syndrome, patients with mycosis fungoides, and healthy volunteers.
Main outcome measures: Programmed death-1 expression on T cells by flow cytometry and interferon γ (IFN-γ) production by enzyme-linked immunosorbent assay.
Results: We report significantly increased PD-1 expression on CD4(+) T cells from patients with Sézary syndrome compared with CD4(+) T cells from patients with mycosis fungoides and healthy volunteers. Both CD26(-) and CD26(+) populations of CD4(+) T cells demonstrated increased expression of PD-1, which was upregulated by the engagement of the T-cell receptor with anti-CD3/CD28 antibodies. In addition, blockade of the signaling pathway with blocking antibodies to PD-1 or its ligand PD-L1 led to an increase in the capacity to produce IFN-γ among some patients. Finally, longitudinal studies of 1 patient revealed a progressive decrease in PD-1 expression on CD4(+) T cells with improvement of clinical disease.
Conclusion: Our data imply that increased PD-1 expression in Sézary syndrome may play a role in attenuating the immune response and provide further insight into the immunosuppressive nature of CD4(+) T cells in Sézary syndrome and suggest another potential means of targeted therapy for these patients.