Notch signaling defects in NK cells in patients with cancer

Zakiryanova, Gulnur K.; Kustova, Elena; Urazalieva, Nataliya T.; Baimukhametov, Emile T.; Makarov, Valeriy; Turaly, Gulmariya M.; Shurin, Galina V.; Biyasheva, Z. M.; Nakisbekov, Narymzhan N.

doi:10.1007/s00262-020-02763-w

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…Moreover, Notch signaling induced T lineage restriction by downregulating C/EBPα and PU.1 in multilineage precursors [25]. These results together with the findings of altered Notch 1 and Notch 2 expression in NK cells in patients with cancer [2,18] justify further analysis of C/ EBPα and PU.1 transcription factors in lymphocytes and hematopoietic precursors isolated from cancer patients. BACH1 and BACH2 (BTB and CNC homology) are transcription repressors that belong to the basic regionleucine zipper family [28].…”

Section: Introductionmentioning

confidence: 88%

“…The hypothesis of intrinsic transcriptional defects in the differentiation mechanism of hematopoietic stem and progenitor cells as a source of dysfunction of immature and mature immune cells in cancer patients is supported by a growing number of recent findings. A significant reduction in c-myc expression was observed in both NK cells and T lymphocytes in patients with cancer [1,2]. There is evidence of a high level of c-myc expression in neutrophils in cancer [3].…”

Section: Introductionmentioning

confidence: 99%

“…As proliferation and differentiation are mutually exclusive, c-myc -a proliferative factor, and C/EBPα -a differentiation factor, work in opposition to each other. Given that c-myc expression is down-regulated in NK and T cells in patients with cancer [1,2,18], this raises an interesting question about C/EBPα activity in different lymphocyte subsets in cancer.…”

Section: Introductionmentioning

confidence: 99%

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Expression of Pu.1, C/Ebp? and Bach1 Transcription Factors in Immune Cells in Patients with Cancer

2021

Journal of Cellular Immunology

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Dysfunction and abnormal differentiation of immune cells and hematopoietic precursors are well described in patients with cancer, although the role of transcription factors in these defects is not well established. Here, we evaluated expression of C/EBPα, PU.1 and BACH1 transcription factors in lymphoid and myeloid cells, including NK cells, T cells, neutrophils and monocytes, isolated from healthy donors and cancer patients. The results revealed a significant suppression of transcription factors participating in the development of immune cells in patients with cancer. Analysis of expression of transcription factors in CD34 + CD45 dim hematopoietic precursors showed that in contrast to the downregulation of transcription factor in mature peripheral blood immune cells, expression of these regulators in stem/precursor cells was significantly increased in patients with lung cancer, especially in patients with detectable metastases. These results open a new opportunity to test whether altered transcriptional regulation of mature immune cells in cancer may be intrinsically related to abnormal functioning of transcription factors in early hematopoiesis or occurs independently via direct effects of tumor-derived factors on circulating immune cells.

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Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of Pu.1, C/Ebp? and Bach1 Transcription Factors in Immune Cells in Patients with Cancer

2021

Journal of Cellular Immunology

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“…Expansion of these studies is well justified as it is conceivable that correction of NK cell molecular defects and functional rescue of NK cells will be great promise for cancer treatment. may also be associated with immune defects in cancer [18]. Analyzing peripheral blood lymphocytes harvested from healthy donor and patients with cancer, the authors revealed a significant reduction of c-myc proto-oncogene expression in both circulating NK and T cells in cancer [19].…”

Section: Lung Cancermentioning

confidence: 99%

“…Finally, studies aiming at identification of potentially inherent or extrinsic tumor-induced immune cell abnormalities in cancer should comprehensively analyze different subsets of lymphocytes and their precursors in patients with different types of cancer and in high cancer risk populations. The studies discussed here [18,19,38,49] represent an example of Notch1/c-Myc signaling evaluation in NK and T cells in cancer. These signaling molecules among other molecules may represent a proper target for immunotherapeutic approach aimed at NK-cell functional repair.…”

Section: Nk Cell Nk Cellmentioning

confidence: 99%

Cancer-associated Molecular Abnormalities in Human NK cells

2021

Journal of Cellular Signaling

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Natural Killer (NK) cells play a key role in the immune responses against infection and cancer as powerful cytotoxic effector cells and regulators of both innate and adaptive immunity [1,2]. Therefore, defects in NK cell functions are important mechanisms for immune evasion of malignant cells [3]. For instance, the ability of tumor cells and tumor-associated stromal/infiltrating cells to inhibit NK cell activity, which results in preventing NK cells from recognizing and killing tumor cells, has been reported for melanoma, neuroblastoma, gastrointestinal sarcoma, hepatocellular cancer (HCC), pancreatic cancer, colorectal carcinoma and other types of cancer [4][5][6][7][8][9]. A potential loss of NK cell numbers and function at preneoplastic stages of tumorigenesis as a possible mechanism for cancer induction and progression has been also recently proposed [5,10]. However, molecular mechanisms regulating NK cell dysfunction and exhaustion in cancer are largely unclear.Furthermore, the link between NK cell deficiency and cancer risk has been also suggested. For instance, the abnormal NK cells and their functional impairment in patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, which contribute to the progression of HCC have been documented [11]. Moreover, comparative mRNA gene expression profiling by wholehuman-genome microarrays combined with phenotypic and functional characterization of circulating NK cells from patients with HCV-related liver cirrhosis and HCC identified energy metabolism and cell motility defects of NK cells as main mechanisms responsible for functional NK cell damage in patients with cancer [12]. Published analysis of the 'omic' data (i.e., tumor RNA-seq and wholeexome sequences of germline genomes) representing 13 common types of cancer showed that people with inherited

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