Decreased number and reduced NKG2D expression of Vδ1 γδ T cells are involved in the impaired function of Vδ1 γδ T cells in the tissue of gastric cancer

Abstract

In cancer patients, impaired function of immune cells--such as CD8(+) T cells, NK cells, and dendritic cells--reportedly results in tumor progression. Although γδ T cells also play a critical role in tumor defense, their function remains unclear in cancer patients. The frequency and function of γδ T cells in peripheral blood, normal gastric mucosa, and cancer tissue were evaluated by multicolor flow cytometry. We also determined NKG2D expression on γδ T cells in gastric cancer patients. The frequency of Vδ1 γδ T cells in gastric cancer tissue is significantly lower than in normal gastric mucosa; however, differences in the frequencies of Vδ2 and Vγ9 γδ T cells between normal gastric mucosa and gastric cancer tissue were not statistically significant. The Vδ1 γδ T cells from gastric cancer tissue produce significantly less IFN-γ than those from normal gastric mucosa do. Expression of NKG2D on Vδ1 γδ T cells from gastric cancer tissue was significantly lower than in normal gastric mucosa. We also found a significant correlation between NKG2D expression and IFN-γ production of Vδ1 γδ T cells in gastric cancer tissue. Vδ1 γδ T cells show decreased frequency and impaired function in gastric cancer tissue, for which decreased NKG2D expression might be one of the mechanisms. Modalities specifically targeting NKG2D in Vδ1 γδ T cells may provide a breakthrough treatment for gastric cancer patients.