TY - JOUR
T1 - The endogenous danger signals HSP70 and MICA cooperate in the activation of cytotoxic effector functions of NK cells
AU - Elsner, Leslie
AU - Flügge, Perris F.
AU - Lozano, Jingky
AU - Muppala, Vijayakumar
AU - Eiz-Vesper, Britta
AU - Demiroglu, Sara Y.
AU - Malzahn, Dörthe
AU - Herrmann, Thomas
AU - Brunner, Edgar
AU - Bickeböller, Heike
AU - Multhoff, Gabriele
AU - Walter, Lutz
AU - Dressel, Ralf
PY - 2010/4
Y1 - 2010/4
N2 - Although natural killer (NK) cells are often described as first line defence 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 major histocompatibility complex class I chain-related molecule A (MICA) in a natural killer group 2 member D (NKG2D-) 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 tumour cells by a histone deacetylase inhibitor and NK cells were activated by HSP70 or TKD, both treatments jointly improved the killing of the tumour 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 tumour cells.
AB - Although natural killer (NK) cells are often described as first line defence 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 major histocompatibility complex class I chain-related molecule A (MICA) in a natural killer group 2 member D (NKG2D-) 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 tumour cells by a histone deacetylase inhibitor and NK cells were activated by HSP70 or TKD, both treatments jointly improved the killing of the tumour 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 tumour cells.
KW - Cancer
KW - Cellular cytotoxicity
KW - Heat shock protein 70
KW - Immunotherapy
KW - NKG2D ligands
KW - Natural killer cells
UR - http://www.scopus.com/inward/record.url?scp=77953946258&partnerID=8YFLogxK
U2 - 10.1111/j.1582-4934.2008.00677.x
DO - 10.1111/j.1582-4934.2008.00677.x
M3 - Article
C2 - 20569278
AN - SCOPUS:77953946258
SN - 1582-1838
VL - 14
SP - 992
EP - 1002
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 4
ER -