Dysregulated Expression of Tim-3 and NKp30 Receptors on NK Cells of Patients with Chronic Lymphocytic Leukemia

Background: In this study, the expression pattern of NKp30 and T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3), as candidates for activating and inhibitory receptors of NK cells, were evaluated in patients with chronic lymphocytic leukemia (CLL). Patients and Methods: 24 CLL patients and 19 healthy controls were enrolled. Fresh peripheral blood was collected from all subjects and stained with fluorochrome-conjugated antibodies. The frequency of CD56+/CD3–/NKp30+ and CD56+/CD3–/Tim-3+ cells was determined by multicolor flow cytometry. Results: Our results revealed that Tim-3 is significantly upregulated on natural killer (NK) cells of CLL patients in comparison to healthy controls. NK cells of CLL patients showed lower expression of NKp30-activating receptor compared to controls. Tim-3 expression pattern on NK cells of CLL patients was correlated with poor prognostic factors including low hemoglobin level, high absolute lymphocyte count, and high serum C-reactive protein level. Conclusion: Dysregulated expression of Tim-3 and NKp30 receptors confirms the exhaustion state of NK cells in CLL. Our data introduce Tim-3 as a promising biomarker and potential target for immunotherapy of CLL.