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Notch signaling defects in NK cells in patients with cancer

Gulnur K Zakiryanova1, Elena Kustova2, Nataliya T Urazalieva2

  • 1Al-Farabi Kazakh National University, Almaty, Kazakhstan. gzakiryanova@gmail.com.

Cancer Immunology, Immunotherapy : CII
|October 21, 2020
PubMed

Insights

Cancer impairs natural killer (NK) cells by altering proto-oncogene expression. Researchers found decreased Notch receptors and increased Cdk6 in NK cells from cancer patients, impacting immune function.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Proto-oncogene dysregulation is implicated in lymphocyte function and autoimmune diseases.
  • Previous work showed decreased c-kit and c-Myc in cancer-associated NK cells, suggesting functional deficits.
  • The tumor microenvironment may influence NK cell proto-oncogene expression.

Purpose of the Study:

  • To investigate the regulatory mechanisms behind altered proto-oncogene expression in NK cells from cancer patients.
  • To determine the expression levels of specific genes (c-Myc, Notch receptors, p53, Rb, Cdk6) in NK cells within the tumor environment.

Main Methods:

  • Isolation of NK cells from healthy donors and cancer patients.
  • Quantitative analysis of c-Myc, Notch1, Notch2, p-53, Cdk6, Rb, and phosphorylated Rb expression.
  • Comparative analysis between NK cells from cancer patients and healthy controls.

Main Results:

  • Significant down-regulation of Notch receptors (Notch1, Notch2) in NK cells from cancer patients.
  • Significant up-regulation of Cyclin-dependent kinase 6 (Cdk6) expression in NK cells from cancer patients.
  • No significant alterations observed in p53 and Rb protein expression levels.

Conclusions:

  • Novel signaling pathways involving Notch receptors and Cdk6 are altered in NK cells within the tumor microenvironment.
  • These findings provide insights into the deregulated proto-oncogene expression in NK cells of cancer patients.
  • Further research is warranted to explore the origins of these alterations across various cancer types.
Keywords:
NK cellsNotch1Notch2T cellsc-myc

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