Notch signaling defects in NK cells in patients with cancer
Zakiryanova G.K. Kustova E. Urazalieva N.T. Baimukhametov E.T. Makarov V.A. Turaly G.M. Shurin G.V. Biyasheva Z.M. Nakisbekov N.N. Shurin M.R.
April 2021Springer Science and Business Media Deutschland GmbH
Cancer Immunology, Immunotherapy
2021#70Issue 4981 - 988 pp.
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.
c-myc , NK cells , Notch1 , Notch2 , T cells
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Al-Farabi Kazakh National University, Almaty, Kazakhstan
Laboratory of Immunology, Scientific Center of Pediatric and Children Surgery, Almaty, Kazakhstan
Department of Oncology, Kazakh Medical University of Continuing Education, Almaty, Kazakhstan
Department of Oncosurgery, Almaty Oncology Center, Almaty, Kazakhstan
Joint Use Center, Atchabarov Scientific Research Institute of Fundamental and Applied Medicine, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
Departments of Pathology and Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
Al-Farabi Kazakh National University
Laboratory of Immunology
Department of Oncology
Department of Oncosurgery
Joint Use Center
Departments of Pathology and Immunology
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