ArticleCell stress & chaperones2015
A hypoxia-induced decrease of either MICA/B or Hsp70 on the membrane of tumor cells mediates immune escape from NK cells.
Article in Cell stress & chaperones, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Hypoxic tumor microenvironment and immune cell dynamics: From metabolic reprogramming to therapeutic innovation.Iranian journal of basic medical sciences · 2026Review
- Tumor hypoxia shapes natural killer cell anticancer activities.Journal of molecular medicine (Berlin, Germany) · 2025Review
- HIF-1α: A Key Factor Mediating Tumor Cells from Digestive System to Evade NK Cell Killing via Activating Metalloproteinases to Hydrolyze MICA/B.Biomolecules · 2025Review
- Recent advances in non-invasiveBiomaterials science · 2025Review
- Decoding iron deficiency in cancer: mechanisms, immune modulation, and therapeutic potential.Frontiers in nutrition · 2025Review
- NK cell exhaustion in the tumor microenvironment.Frontiers in immunology · 2023Review
- NK cells and solid tumors: therapeutic potential and persisting obstacles.Molecular cancer · 2022Review
- Molecular Mechanisms of Epigenetic Regulation, Inflammation, and Cell Death in ADPKD.Frontiers in molecular biosciences · 2022Review
- Role of NK Cells in Tumor Progression.Experientia supplementum (2012) · 2022Article
- Tumor microenvironment and immune evasion in head and neck squamous cell carcinoma.International journal of oral science · 2021Review
- Hypoxia-mediated down-regulation of miRNAs' biogenesis promotes tumor immune escape in bladder cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- Flipside of the Coin: Iron Deficiency and Colorectal Cancer.Frontiers in immunology · 2021Review
- Tumor hypoxia: an important regulator of tumor progression or a potential modulator of tumor immunogenicity?Oncoimmunology · 2021Article
- Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression.Journal of experimental & clinical cancer research : CR · 2020Article
- Hypoxia regulates the differentiation and anti-tumor effector functions of γδT cells in oral cancer.Clinical and experimental immunology · 2020Article
- Inhibiting exosomal MIC-A and MIC-B shedding of cancer cells to overcome immune escape: new insight of approved drugs.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2019Article
- Hypoxia-induced shedding of MICA and HIF1A-mediated immune escape of pancreatic cancer cells from NK cells: role of circ_0000977/miR-153 axis.RNA biology · 2019Article
- Genetic determinants and an epistasis ofProceedings of the National Academy of Sciences of the United States of America · 2018Article
- microRNA-889 is downregulated by histone deacetylase inhibitors and confers resistance to natural killer cytotoxicity in hepatocellular carcinoma cells.Cytotechnology · 2018Article
- Exosome-related tumor microenvironment.Journal of Cancer · 2018Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent findings suggest that hypoxia of the tumor microenvironment contributes to immune escape from natural killer (NK) cell-mediated cytotoxicity. Heat shock protein 70 (Hsp70) and the stress-regulated major histocompatibility class I chain-related protein A and B (MICA/B) both serve as ligands for activated NK cells when expressed on the cell surface of tumor cells. Herein, we studied the effects of hypoxia and hypoxia-inducible factor-1α (HIF-1α) on the membrane expression of these NK cell ligands in H1339 with high and MDA-MB-231 tumor cells with low basal HIF-1α levels and its consequences on NK cell-mediated cytotoxicity. We could show that a hypoxia-induced decrease in the membrane expression of MICA/B and Hsp70 on H1339 and MDA-MB-231 cells, respectively, is associated with a reduced sensitivity to NK cell-mediated lysis. A knockdown of HIF-1α revealed that the decreased surface expression of MICA/B under hypoxia is dependent on HIF-1α in H1339 cells with high basal HIF-1α levels. Hypoxia and HIF-1α did not affect the MICA/B expression in MDA-MB-231 cells but reduced the Hsp70 membrane expression which in turn also impaired NK cell recognition. Furthermore, we could show that the hypoxia-induced decrease in membrane Hsp70 is independent of HIF-1α in MDA-MB-231. Our data indicate that hypoxia-induced downregulation of both NK cell ligands MICA/B and Hsp70 impairs NK cell-mediated cytotoxicity, whereby only MICA/B appears to be regulated by HIF-1α.
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