CD4 +CD25 + Regulatory T Cells Decreased the Antitumor Activity of Cytokine-Induced Killer (CIK) Cells of Lung Cancer Patients
CD4 +CD25 + regulatory T cells (Tregs) have been shown to inhibit cytotoxic lymphocytes-mediated immune responses. Cytokine-induced killer (CIK) cells exert high impact on adoptive immunotherapeutic approaches. Therefore, the purpose of this report was to determine the effect of Tregs on CIK cell growth and CIK-induced cytotoxicity for inhibition of tumor growth in vivo as well as in vitro. After depletion of CD4 +CD25 + cells before culture, the proliferation and cytotoxicity of CIK cells, which indicated in bromodeoxyuridine (BrdU) and lactic dehydrogenase (LDH) assays, were significantly increased. Depletion of CD4 +CD25 + cells preculture also enhanced the suppression effect on the lung cancer cells inoculated in experimental animals. Blockage of glucocorticoid-induced tumor necrosis factor receptor (GITR) and transforming growth factor β1 (TGF-β1) by antibodies partially abrogated the suppressive effect of CD4 +CD25 + cells on CIK. These results indicated that Tregs could inhibit the antitumor activity of CIK cells. The molecules TGF-β and GITR may contribute to the suppressive function of CD4 +CD25 + cells.
KEY WORDS:CD4+CD25+ regulatory T cells CIK GITR TGF-β
We thank Dr. Yan Fang, Department of Pediatrics Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine for providing help and assistance for this paper.
- 9.Ren X, Yu J, Liu H, et al.: Th1 bias in PBMC induced by multicycles of auto-CIKs infusion in malignant solid tumor patients. Cancer Biotherapy & Radiopharmaceuticals 2006; 21(1):22–33Google Scholar
- 10.Schmidt-Wolf IGH, Lefterova P, Mehta BA, et al.: Phenotypic characterization and identification effector cells involved in tumor cells recognition of cytokine-induced killer cells. Exp Haematol 21:1673–1679, 1993Google Scholar