肝纖維化對肝浸潤T細胞活化的影響
Date Issued
2004
Date
2004
Author(s)
陳健弘
DOI
922314B002144
Abstract
In 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.
Subjects
Hepatocellular carcinoma
tumor-infiltrating lymphocyte
liver-infiltrating lymphocyte
phenotypes
CD25
fibrosis
Publisher
臺北市：國立臺灣大學醫學院內科
Type
report
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