Figure 1.

Dual role of MICA/B as target molecule for immunosurveillance by NK cells and as mediator of tumor immune escape. MICA/B expressed on the cell surface of tumor cells can be recognized by NK cells through NKG2D and promote a cytotoxic response that leads to tumor cell elimination (immunosurveillance). However, MICA/B can associate with the ERp5 chaperone and, through a proteolytic cleavage mediated by ADAM10, ADAM17 and MMP14, generate sMICA/B that promote NKG2D down-regulation and impairment of NK cell-effector functions, thus facilitating tumor immune escape (immunoevasion).