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Schilling, D. ; Tetzlaff, F.* ; Konrad, S.* ; Li, W.* ; Multhoff, G.

A hypoxia-induced decrease of either MICA/B or Hsp70 on the membrane of tumor cells mediates immune escape from NK cells.

Cell Stress Chaperones 20, 139-147 (2014)
DOI
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Hif-1α ; Hsp70 ; Hypoxia ; Immune Escape ; Mica/b ; Nk Cell
ISSN (print) / ISBN 1355-8145
e-ISSN 1466-1268
Journal Cell Stress and Chaperones
Quellenangaben Volume: 20, Issue: 1, Pages: 139-147 Article Number: , Supplement: ,
Publisher Springer
Reviewing status Peer reviewed
Institute(s) Institute of Biological and Medical Imaging (IBMI)