Numbers of CD8+PD-1+ and CD4+PD-1+ Cells in Peripheral Blood of Patients with Chronic Lymphocytic Leukemia Are Independent of Binet Stage and Are Significantly Higher Compared to Healthy Volunteers.

ABSTRACT

The programmed cell death pathway is involved in functional impairment of cytotoxic CD8+ T cells in chronic viral infection and in tumor immune evasion. The interaction of programmed cell death-1 (PD-1) with its ligand suppresses antitumor T cell function and stimulates the regulatory T cell population. The objectives were to investigate whether examining PD-1 expression in peripheral T cells of patients with chronic lymphocytic leukemia (CLL) reflected the disease phase and Binet stage and to compare the results with those in healthy volunteers. The study analyzed peripheral blood from previously untreated patients with CLL, patients with relapsed or refractory disease under treatment and healthy blood donors using flow cytometry. PD-1 expression in peripheral blood CD4+ and CD8+ cells was markedly different between disease stages and in comparison with healthy subjects. The highest numbers of both CD8+PD-1+ and CD4+PD-1+ cells were present in patients with relapsed/refractory disease. No distinct difference according to Binet stage was found. These facts support the hypothesis that tumor clones may switch effector CD8+ cells through the PD-1/PD-1L pathway into an immunotolerant state. The extent to which the mechanisms of antitumor immunity are influenced by enhanced expression of the programmed cell death depends on the disease phase but not Binet stage.