| Liver cancer is a common malignancy, ranking the second cause for deaths of all malignant tumors in China since the end of the 20th century, depriving 20.30/100,000 lives. With the wide-spread use of B ultrasonography, CT and MRI in recent years and use of α-fetal protein (AFP) as an indicator for liver cancer, the diagnostic rate of liver cancer has been raised greatly. In addition, there have been versatile therapeutic modalities for liver cancer, forming a series of synthetic protocols with surgery as the mainstay of treatment. Nevertheless, miltifocal nature and intrahepatic metastasis of liver cancer render it difficult for surgery to resect the tumor tissue completely; some tumor foci are inoperable because of size or location. Furthermore, liver cancer is less sensible to radiotherapy and chemotherapy, whose adverse and toxic effects often cause serious impairment, lowering the quality of life or even threatening life of the patients. Drug resistance of tumor cells is also a significant factor affecting the outcome. Apparently, the conventional therapies for liver cancer have certain limitations. The main reason is that the recurrence rate of liver caner is very high; the 5-year postoperative recurrence rate is about 80 percent for large liver cancers and 60 percent for small ones. There are no effective regimens of preventing recurrence of liver cancer at present, and therefore developing a new remedy of preventing recurrence is of great significance in raising the therapeutic level of liver cancer. Tumor immunotherapy is a research subject that attracts much attention. Although there have been reports about clinical use of non specific immune stimulants, cytokines (IL-2, INF-γ), LAK and TIL, the overall outcome was not satisfactory. Of course, these treatments can raise specific anti-tumor immune response of the organism to some extent, but they lack effective induction of a specific tumor-killing mechanism, and therefore how to induce the organism to produce a specific tumor-killing mechanism has become a heat point of research in recent years. Cell-mediated immunity plays an essential role in specific anti-tumor immune reaction. As activated T cell is an important effector cell, achieving large amounts of activated T cells is the crux for success of immunotherapy. Based on multi-signal stimulation of T cell activation, our previous studies established the method of inducing liver cancer cell toxin T lymphocytes (CTL)in vitro, i.e. using surgically resected liver cancer specimens to separate tumor cells and tumor infiltrating lymphocytes, and then co-cultivated them in vitro to activate the lymphocytes under the cross linking action of anti CD28 co-stimulating molecules. Both in vivo and ex vivo studies proved that the activated T cellss obtained in this way was superior to the existing non specific anti-tumor actions, but it is difficult to obtain T cells in vitro in large amounts and in a short period. In addition, not all specimens can be cultivated in vitro successfully. Even if T cell cultivation is successful, it is applicable to only a few patients clinically. These are problems we intend to resolve in the present study, and previous studies on the role of Fas-FasL in anti-tumor immunity provide us with a deeper understanding of these problems. Fas is a type-I membrane protein belonging to the TNF/NGF receptor family. Human lymphocyte expresses Fas. It has been demonstrated that when lymphocyte is activated, Fas expression increases and sensitivity to Fas-mediated cell apoptosis also increases. Fas ligand (FasL) does not express in normal lymphocyte but does when lymphocyte is activated. Fas-FasL combination is able to transmit apoptotic signals to cells via the death domain (DD) of the Fas receptor intracellular region, inducing expression of Fas receptor cell apoptosis. Therefore, combination of activated T cells with Fas may induce apoptosis of the activated T cells. This is one of the mechanisms of immunoregulation of the normal organism, whereby over immune re... |
PDF Full Text Request