陳健弘2006-07-262018-07-112006-07-262018-07-112004http://ntur.lib.ntu.edu.tw//handle/246246/23637In our previous study, we investigated the phenotypic analysis of tumor-infiltrating lymphocytes (TILs) in HCC tissues and the corresponding non-tumor liver tissues infiltrating lymphocytes (NILs). We found that Most of infiltrating lymphocytes from the HCC tissues and the corresponding non-tumor liver tissues were activated and expressed antigen-experienced phenotypes. Around 70%-90% NILs or TILs expressed the antigen-experienced or memory phenotypes of CD45RA- / CD45RO+ / CD62L-. Around 60%-70% CD4+ or CD8+ NILs and TILs expressed the activation markers CD69 and HLA-DR. However, we found that CD25 is under-expressed in both the NILs and TILs. Only 1.0% of the CD8+ NILs and 7.7% of CD8+ TILs expressed CD25 and 11.2% of CD4+ NILs and 28.2% CD4+ TILs expressed CD25. The downregulation of CD25 in NILs might suggest “immune escape” happens not only in the tumors, but also in the diseased liver. It has been shown that CD25 downregulation in TILs is probably caused by matrix metalloproteinases (MMPs). Around 60%-85% of HCC patients have underlying liver cirrhosis. In the 15%-40% HCC patients with non-cirrhotic liver, various degrees of fibrosis can also be detected in the non-tumor liver portions. Accumuating data demonstrated that the MMPs play important roles in the hepatic fibrogenesis. Thereore, if the MMPs secreted by the tumor cells can degrade CD25 expressed on the TILs, we would wonder whether the MMPs activated in the hepatic fibrosis can also degrade CD25 expressed on the liver-infiltrating lymphocytes of fibrotic livers. Thus, our hypothesis generated from our previous study is: the liver-infiltrating lymphocytes are chronically activated. The liver-infiltrating lymphocytes will express the actiavation markers of HLA-DR, CD25, and CD69. In the process of hepatic fibrosis, the CD25 is downregulated because of something activated, such as MMPs, can downregulate the CD25. The existence of hepatic tumors will have further influences on the expressions of CD25. In this current project, we used the murine model of hepatic fibrosis. We successfully grew the HCC tumors in the fibrotic livers in the murine models. We found that the MMP-2 expressions were upregulated and activated in the fibrotic livers. However, there were no significant differences in the CD25 expressions on the liver-infiltrating lymphocytes between the fibrotic livers and control livers. Thus, it was possible that the low expression of CD25 on the liver-infiltrating lymphocytes was not directly related the MMPs in the fibrotic livers.application/pdf756077 bytesapplication/pdfzh-TW國立臺灣大學醫學院內科Hepatocellular carcinomatumor-infiltrating lymphocyteliver-infiltrating lymphocytephenotypesCD25fibrosisreporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/23637/1/922314B002144.pdf