Abstract
Objective To investigate the regulation of CCL22/CCR4 signaling on CD4+ CD25+ regulatory T cells (Tregs) and immune escape in hepatocellular carcinoma (HCC). Methods CCL22, interleukin-2 (IL-2), transforming growth factor-β (TGF-β), and interleukin-10 (IL-10) levels in tumor tissue of 30 HCC patients were determined by ELISA. Tumor infiltrating lymphocytes were isolated and assayed by flow cytometry to evaluate the change of CD4+ CD25+ Tregs in tumor tissue, and CCR4 in CD4+ CD25+ Tregs were detected. Results The CCL22 level in tumor tissue was obviously increased. The level of CCL22 in tumor tissue was (920.1±180.1)ng/L, which was significantly higher than that in non-tumor tissue[(227.2±108.6) ng/L; P<0.05]. The tumor infiltrating CD4+ CD25+ Tregs was obviously increased, reaching approximately to (13.3±4.0)%, and the CCR4 expression in CD4+ CD25+ Tregs increased to (8.8±3.0)%. Along with progression in clinical TNM staging, the levels of CD4+ CD25+ Tregs and CD4+ CD25+ CCR4+ Tregs in tumor tissue increased, and were correlated with the CCL22 level. IL-2 level in tumor tissue was decreased, but TGF-β and IL-10 levels were increased. HCC tissue can secrete a large amount of CCL22 that could recruit CD4+ CD25+ Tregs to tumor tissue by activating CCL22/CCR4 signaling. CD4+ CD25+ Tregs played an important role in the immune escape of HCC by releasing plenty of TGF-β and IL-10 and inhibiting IL-2 secretion. Conclusion This study validates CCL22/CCR4 as therapeutic targets in immunotherapy for HCC. Key words: Hepatocellular carcinoma; Regulatory T cells; Immune escape
Published Version
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