As such, NK cells in patients with B-CLL will be exposed continually to tumor cells within the circulatory system where chronic signaling interactions, such as tumor cell expressing and shedding NKG2D and NCR ligands, will lead to NKG2D downregulation and potential NK ‘exhaustion’ [14, 34]. The gene discussed is KLRK1; the disease is B-cell chronic lymphocytic leukemia.