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The endogenous danger signals HSP70 and MICA cooperate in the activation of cytotoxic effector functions of NK cells.
J. Cell. Mol. Med. 14, 992-1002 (2010)
Although natural killer (NK) cells are often described as first line defense against infected or malignant cells which act without the need of prior activation, it is known now that the NK cell activity is tightly regulated by other cells and soluble factors. We show here that the stress-inducible heat shock protein (HSP) 70 activates human NK cells to kill target cells expressing MICA (major histocompatibility complex class I chain-related molecule A) in a NKG2D (natural killer group 2 member D) dependent manner. The HSP70-derived peptide TKD (TKDNNLLGRFELSG) was able to replace the full-length HSP70 and to exert the same function. Interestingly, the expression of the cytotoxic effector protease granzyme B in NK cells was increased after TKD-stimulation. When MICA and MICB expression was induced in human tumor cells by a histone deacetylase inhibitor and NK cells were activated by HSP70 or TKD, both treatments jointly improved the killing of the tumor cells. Thus, the synergistic activity of two stress-inducible immunological danger signals, HSP70 and MICA/B, leads to activation and enhanced cytotoxicity of human NK cells against tumor cells.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
heat shock protein 70; NKG2D ligands; natural killer cells; cellular cytotoxicity; cancer; immunotherapy
ISSN (print) / ISBN
1582-1838
e-ISSN
1582-4934
Quellenangaben
Volume: 14,
Issue: 4,
Pages: 992-1002
Publisher
Blackwell
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CCG Innate Immunity in Tumor Biology (PATH-KTB)