Reduced Expression of Natural Killer Cell-Related Activating Receptors by Peripheral Blood Mononuclear Cells from Patients with Breast Cancer and Their Improvement by Zoledronic Acid

Asian Pac J Cancer Prev. 2022 May 1;23(5):1661-1669. doi: 10.31557/APJCP.2022.23.5.1661.

Abstract

Background/aim: Natural killer (NK) cell receptors affect the NK cell-mediated elimination of malignant cells. In this experimental study the effect of Zoledronic acid (ZOL) was investigated on the expression of NK activating- (NKP46 and NKG2D) and inhibitory (KIR2DL1) receptors by Phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from breast cancer (BC) patients.

Materials and methods: Peripheral blood mononuclear cell-extracted RNA from thirty breast cancer women and twenty-five healthy subjects was analyzed for gene expression of NKP46, NKG2D and KIR2DL1 using real time-PCR. Then, the PBMCs from BC patients were cultured in the presence of PHA with 5 μg/ml, 10 or 20 μg/ml of ZOL for 32 hours and expression of the aforementioned receptors was determined.

Results: Expression of NKP46, NKG2D and NKP46/KIR2DL1 ratio in BC women were lower than healthy group (P<0.01, P<0.04 and P<0.05, respectively). NKP46 expression was up-regulated by PHA-stimulated PBMCs treated with 10 μg/ml and 20 μg/ml of ZOL compared with PHA-stimulated cultures (P<0.01 and P<0.05, respectively). NKG2D expression remarkably increased by PHA-stimulated cultures treated with 5 μg/ml, 10 μg/ml and 20 μg/ml of ZOL compared with PHA-stimulated cultures (P<0.05 and P<0.02 and P<0.04, respectively).

Conclusion: Expression of NK cell-related activating receptors decreased in BC patients. ZOL can improve the expression of NK activating receptors.

Keywords: Immunomodulation; NK cell receptors; cancer; immune system.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Female
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • NK Cell Lectin-Like Receptor Subfamily K* / metabolism
  • Natural Cytotoxicity Triggering Receptor 1* / metabolism
  • Phytohemagglutinins / pharmacology
  • Receptors, KIR2DL1* / metabolism
  • Receptors, Natural Killer Cell / metabolism
  • Zoledronic Acid* / therapeutic use

Substances

  • KIR2DL1 protein, human
  • KLRK1 protein, human
  • NCR1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Natural Cytotoxicity Triggering Receptor 1
  • Phytohemagglutinins
  • Receptors, KIR2DL1
  • Receptors, Natural Killer Cell
  • Zoledronic Acid