Interleukin-6 Inhibits Regulatory T Cells and Improves the Proliferation and Cytotoxic Activity of Cytokine-induced Killer Cells

Abstract

The presence of regulatory T cells in patients who received therapeutic cytokine-induced killer (CIK) cells may inhibit host immunity, leading to failed immunotherapy. In this study, we investigated the impact of using interleukin-6 (IL-6) on the phenotype alteration, proliferation, and cytotoxic activity of CIK cells generated from the peripheral blood mononuclear cells of patients with hepatocellular carcinoma. We found that addition of IL-6 to CIK-cell culture medium decreased the percentage of Treg/CD4+, Treg/CD3+ T cells in the resultant CIK cells and simultaneously increased the proliferation ability, the expression of CD45RO+CD62LlowCCR7low effector memory phenotype, and cytotoxicity of the CIK cells against hepatocellular carcinoma in vitro. Our results also showed that the percentage of Th17/CD4+ cells was increased in CIK cells, but the proportion of Th17/CD4+ cells was not affected by the addition of IL-6 to CIK-cell culture medium. Collectively, these data suggest that IL-6 may have the potential to improve antitumor activity of CIK cells in cancer immunotherapy.