Ligand hides tumors from attack

A tumor-derived soluble ligand impairs expression of NKG2D and subsequent T-cell activation.

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Tumor cells display surface molecules that should identify them as abnormal, but still they evade the body's immune response through mechanisms that have been unclear. In October 17 Nature, Veronika Groh and colleagues at the Fred Hutchinson Cancer Research Center, Seattle, Washington, USA, show that a tumor-derived soluble ligand (MIC) — usually induced by stress — impair expression of the specific receptor NKG2D and T-cell activation (Nature, 419:734-738, October 17, 2002).

Groh et al. examined NKG2D expression on CD8+ T cells among tumor infiltrating lymphocytes extracted from epithelial tumors. They observed that expression of NKG2D is markedly reduced on large numbers of tumor-infiltrating and matched peripheral blood T cells isolated from individuals with cancer. In addition, this systemic deficiency is associated with circulating tumor-derived soluble MICA, causing the downregulation of NKG2D and subsequently the severe impairment of the responsiveness of tumour-antigen-specific effector T cells.

"We therefore have a new hint ...

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