Tumor modulation of T-helper cytokine secretion (49.6)

Abstract

Abstract Tumor modulation of T-cells contributes to tumor-induced immune suppression. To determine if tumor-derived factors selectively recruit T-cell subpopulations, the migration of T-cells in response to SCC VII/SF or epithelial cell (epi)-conditioned media (CM) was determined by Transwell chemotaxis assay. Increased levels of CD4+CD25+ cells were observed in T-cells migrating in response to SCC-CM. Following stimulation, T-cells migrating in response to SCC-CM had diminished IFN-γ secretion as compared to epi-CM. Additional studies determined whether SCC-CM actively suppresses IFN-γ secretion by Th1 cells in the tumor microenvironment. Th1 and Th2 cells were differentiated from naïve lymph node cells then cultured with SCC or epi-CM. After overnight stimulation, IFN-γ and IL-10 secretion was assessed by ELISA. Following SCC-CM treatment, IFN-γ secretion by Th1 cells was diminished as compared to epi-CM treatment. IL-10 secretion by Th2 cells treated with either CM was unaffected. The effects of SCC-CM on IFN-inducible chemokines are currently under investigation. These results identify mechanisms of tumor-induced immune suppression by demonstrating that Th2 cells are selectively recruited in response to SCC-derived factors and that Th1 cells in the tumor microenvironment have suppressed IFN-γ secretion. Supported by Dept. of Veterans Affairs, American Cancer Society and National Cancer Institute.