| The various strategies of tumor therapy share a common goal: to propel the tumor cell into apoptosis, and at the same time, to augment the cytotoxicity of tumor specific immune cells, such as cytotoxic T lymphocytes (CTL). Two death signal pathways have been identified to control the apoptosis of cell, the mitochondria C pathway and the death receptor pathway. FasL/Fas system is the typical death pair initiating death receptor pathway. Though the two molecules were discovered a decade years ago, recent findings suggest that they have not been thoroughly understood, especially on the tumor cells. It was believed that Fas gene was constitutively expressed on almost all kinds of somatic cells as a "death switch" while expression of Fas ligand (FasL) gene was strictly controlled. It's only expressed on activated mature immune cells, such as T lymphocyte and parts within the immune privilege sites, such as the testis and the eye. FasL/Fas death way was believed to play an essential role in the cytotxoicity of TIL against tumor cell with granzyme/perforin performed as another important killing mechanism. Thus anti-tumor immune would be affected if FasL were neutralized. However, FasL protein is now detectable on the membrane surfaces of several kinds of tumor cells meaning that tumor cell might fight back! By RT-PCR and immunohistochemistry stain FasL mRNA and protein were detectable on the samples of NSCLC surgically resected. Could lung cancer cell perform the autocrine or paracrine apoptosis through FasL/Fas death way? What effects would be exactly imposed upon TIL's cytotoxixity if FasL were neutralized? Would the microenvironment regulate the expression and function of tumor FasL protein and how? There is no doubt that the answers to these questions would deepen our knowledge on the biological behavior of malignant cells in which FasL may play an interesting role. The following is a brief summary of our research.1. Expression of FasL mRNA and Protein on NSCLCRT-PCR and immunohistochemistry stain were performed to detect the expression of FasL mRNA and protein on 40 samples of NSCLC surgically resected. Expression of FasL mRNA and protein were both found to be specifically up regulated in tumor tissues compared with normal control (p<0.01). On tumor tissues, the positive rate of FasL mRNA was 77.5%, significantly higher than that of 10.0% on the normal control (P<0.01). The mean positive percentage of FasL protein on tumor tissues was 62.7±29.1%. Thirty-seven of the 40 tumor samples (92.5%) had the positive percentage above 10%, 26 (65.0%) above 60%, and 19 (47.5%) above 80%. Only 3 (7.5%) of the 40 normal control samples had the positive percentage above 10%, significantly lower than that of the tumor samples (P<0.01). The pulmonary adenocarcinoma had a significantly higher FasL protein positive percentage of 74.3%+21.8% than that of 54.9+31.1% on the squamous cell carcinoma (P<0.05). The density of the passive stain was prominently higher on the marginal tumor cells than those within the tumor mass. Neither FasL mRNA expression nor protein expression varied significantly in tumor's pTNM stages and differentiation degrees (P>0.05). 2. Effects Imposed upon the Viability of Cultured NSCLC Cells whenFasL neutralizedSince Fas could be constitutively expressed on the membrane surface of lung cancer cell NOK-1 (mouse anti-human FasL monoclonal antibody, IgG1) was adopted to block the postulated autocrine and paracrine apoptosis in tumor cell through FasL/Fas death pathway. If the postulated autocrine and paracrine apoptosis did exist the viability of cancer cell would increase when FasL was neutralized by NOK-1.Otherwise its viability would decrease or unchange. In our in-vitro tests, neutralization of FasL did not show significant effect on the viability of tumor cells (P>0.05).3. Effects Imposed upon TIL's Cytotoxicity when FasL NeutralizedThree testing groups were set in this in-vitro tests simulating three different modalities of tumor adoptive immune therapy (AIT). Group A represented the ro...
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