CCL22/CCR4 signaling induces immune escape in hepatocellular carcinoma
10.3760/cma.j.issn.1007-8118.2016.01.007
- VernacularTitle:CCL22/CCR4信号通路在原发性肝癌局部免疫逃逸中的作用
- Author:
Shuiming JIANG
;
Haiming LU
;
Lei LIU
;
Qishun ZHANG
- Publication Type:Journal Article
- Keywords:
Hepatocellular carcinoma;
Regulatory T cells;
Immune escape
- From:
Chinese Journal of Hepatobiliary Surgery
2016;22(1):24-26
- CountryChina
- Language:Chinese
-
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.
