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

Oncol Res Treat. 2019;42(4):202-208. doi: 10.1159/000497208. Epub 2019 Mar 14.

Abstract

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.

Keywords: Chronic lymphocytic leukemia; NK cells; NKp30; Tim-3.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Female
  • Gene Expression Regulation / physiology*
  • Hepatitis A Virus Cellular Receptor 2 / metabolism*
  • Humans
  • Killer Cells, Natural / metabolism*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • Male
  • Middle Aged
  • Natural Cytotoxicity Triggering Receptor 3 / metabolism*

Substances

  • Hepatitis A Virus Cellular Receptor 2
  • Natural Cytotoxicity Triggering Receptor 3