NKG2D+CD4+ T Cells with Immune Suppressive Property Increase in Patients with Colorectal Cancer

Some studies suggest that small populations of CD4+ T cells with activation-independent, constitutive, NKG2D expression are found in normal peripheral blood and have immune suppressive properties. The present study was designed to investigate NKG2D expression on CD4+ T lymphocytes and its relationship to immune evasion in colorectal cancer patients. We examined NKG2D expression on both circulating and tumor infiltrating CD4+ and CD8+ T cells or NK cells and evaluated it by multicolor flow cytometry. Furthermore, intracellular cytokine staining was carried out to determine the cytokine profile of NKG2D+CD4+ T cells in colorectal cancer patients. As a result, NKG2D expression on circulating and tumor-infiltrating CD8+ T cells and NK cells was downregulated in colorectal cancer patients. On the other hand, circulating and tumor-infiltrating NKG2D+CD4+ T cells increased in colorectal cancer patients. NKG2D+CD4+ T cells produced more immune suppressive cytokines, such as interleukin-10 and transforming growth factor-1β, than did NKG2D-CD4+ T cells. Increased NKG2D+CD4+ T cells as well as decreased NKG2D expression on CD8+ T cells and NK cells may be one of the key mechanisms responsible for immune evasion by tumors in colorectal cancer.