Notch signaling defects in NK cells in patients with cancer

Cancer Immunol Immunother. 2021 Apr;70(4):981-988. doi: 10.1007/s00262-020-02763-w. Epub 2020 Oct 21.

Abstract

Altered expressions of proto-oncogenes have been reported during normal lymphocytes mitogenesis and in T and B lymphocytes in patients with autoimmune diseases. We have recently demonstrated a significantly decreased expression of c-kit and c-Myc in NK cells isolated from patients with cancer, which might be related to the functional deficiency of NK cells in the tumor environment. Here, focusing on the regulatory mechanisms of this new clinical phenomenon, we determined expression of c-Myc, Notch1, Notch2, p-53, Cdk6, Rb and phosphorylated Rb in NK cells isolated from the healthy donors and cancer patients. The results of our study revealed a significant down-regulation of expression of Notch receptors and up-regulation of Cdk6 expression in NK cells in cancer, while no significant changes in the expression of p53 and Rb proteins were seen. These data revealed novel signaling pathways altered in NK cells in the tumor environment and support further investigation of the origin of deregulated expression of proto-oncogenes in NK cells patients with different types of cancer.

Keywords: NK cells; Notch1; Notch2; T cells; c-myc.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cyclin-Dependent Kinase 6 / genetics
  • Cyclin-Dependent Kinase 6 / metabolism*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Male
  • Middle Aged
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Prognosis
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*
  • Receptor, Notch2 / genetics
  • Receptor, Notch2 / metabolism*
  • Signal Transduction

Substances

  • Biomarkers, Tumor
  • NOTCH1 protein, human
  • NOTCH2 protein, human
  • Receptor, Notch1
  • Receptor, Notch2
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6