Decreased NKG2D expression on NK cells correlates with impaired NK cell function in patients with gastric cancer

Although malignant diseases are known to be associated with immune suppression, the detailed mechanisms involved are still unknown. NKG2D is an activating cell surface receptor expressed by natural killer (NK) cells and CD8+ T cells, and the engagement of NKG2D is extremely important for NK cell activation. Although decreased NKG2D expression on NK cells is closely related to immune evasion by some cancers, the immunopathological importance of this phenomenon in gastric cancer patients remains unclear. NKG2D expression on NK cells was determined, using multicolor flow cytometry, to investigate the mechanisms responsible for immune evasion in gastric cancer patients. NKG2D expression on NK cells from gastric cancer patients was significantly lower than that in healthy controls. Also, NKG2D expression in advanced gastric cancer was significantly lower than that in early gastric cancer. NK cells from patients with lymph node metastasis expressed significantly lower levels of NKG2D than the NK cells from those without lymph node metastasis, and NKG2D expression on NK cells in gastric cancer tissue was significantly lower than that of circulating NK cells. NKG2D expression on NK cells obtained from cancer patients was restored after 48 h in culture with RPMI containing 10% AB serum. Furthermore, NKG2D expression on NK cells obtained after surgery was significantly higher than that before surgery. Decreased NKG2D expression on NK cells may be one of the key mechanisms responsible for NK cell dysfunction in gastric cancer.