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Cutting Edge |
* Department of Internal Medicine II, University Hospital and
Department of Immunology, Eberhard-Karls-University, Tubingen, Germany
The immunoreceptor NKG2D stimulates tumor immunity through
activation of CD8 T cells and NK cells. Its ligand MICA has been
shown to be broadly expressed on human tumors of epithelial origin.
MICA expression correlates with an enrichment of V
1 T cells in tumor
tissue. We report that human tumor cells spontaneously release a
soluble form of MICA encompassing the three extracellular domains,
which is present at high levels in sera of patients with
gastrointestinal malignancies, but not in healthy donors. Release of
MICA from tumor cells is blocked by inhibition of metalloproteinases,
concomitantly causing accumulation of MICA on the cell surface.
Shedding of MICA by tumor cells may modulate NKG2D-mediated tumor
immune surveillance. In addition, determination of soluble MICA levels
may be implemented as an immunological diagnostic marker in patients
with epithelial malignancies.
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