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Effect Of NSCLC Expressing FasL On TILs And Detection Of SFas And SFasL In Serum

Posted on:2005-09-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:G Q ZhangFull Text:PDF
GTID:1104360125965370Subject:Surgery
Abstract/Summary:PDF Full Text Request
Fas (APO-1, CD95) is a type â…  integral membrane protein initially identified by mAbs that induce apoptotic cell death upon binding to certain tumor cells. Molecular cloning of Fas revealed that it belongs to the TNF receptor family and transduces a death signal. Fas is expressed on actived lymphocytes and in various tissues, including the liver, lung and skin. Molecular cloning of Fas ligand (FasL) revealed that it is type â…¡ integral membrane protein. FasL is expressed on actived T and NK cells, and mediates Fas+ target cell lysis by these effector cells. In tumor immune, people usually regarded Fas-FasL pathway as an important mechanism of CTL killing tumor cells, however, recenthy some study discovery that some tumor cells such as hepatocellular cancer and colon cancer can express FasL too, but they didn't mediated self-cells apoptosis and can attack actived TIL through FasL-Fas pathway. It is a new mechanism of tumor immune escape, this study of counterattack mechanism maybe is a new pathway of immune therapy of tumor. The study of immune therapy of tumor have been concentrating on how to active lymphocytes especially T lymphocytes from long time ago, but actived T lymphocytes more easily are attacked from tumor cells than those still T lymphocytes, Because Fas expression of their membrane surface go up. For these reason, we belive that immune therapy will be defated if don't overcome the counterattack from tumor cells, anti-FasL body can conjugate with FasL competited with Fas and effectively block FasL-Fas pathway transduceing a death signal, therefore, anti-FasL body can protect T lymphocytes against immune counterattack from tumor cells.Based on the above theory, some scholars have observed the presence of the counterattack through animal experiment, but the study of expressions only limited at the local position in clinical research, so we intent to isolate and culture lymphocytes and tumor cells from the resected tumors of patients with lung carcinoma, we regard tumor cells as effector cells and lymphocytes as targets, observing the counterattack of tumor cells against lymphocytes, we belive it is more close to clinical reality.Based on the above detail, we want to explore anti-FasL body as a protect factor for immunotherapy in the treatment of lung cancer and its possible use in clinic as following: (1) Detect the expression of FasL in lung adenocarcinoma cells (non-small-cell lung cancer, NSCLC) and A549 lung adenocarcinoma cell line and explore its clinical significance; (2) Detect the counterattack of lung adenocarcinoma cells and A549 against TILs and protected effect of FasL to TILs; (3) Detect the levels of serum sFas and sFasL by sandwich ELISA of 18 cases primary lung carcinoma patients, and explore its clinical significance.In our present study we found the following results: (1) FasL expression rate was 80.2% in 8 cases lung adenocarcinoma, and it was 68.4% in 8 cases A549 lung adenocarcinoma cell line; (2) lung adenocarcinoma cells and A549 cells can attack TILs from primary lung carcinoma to varying degrees in 8 cases, but their attack against TILs descended after anti-FasL body blocking FasL, different both groups is significantly (P<0.05); (3) The levels of sFas and sFasL was higher in 18 cases primary lung carcinoma. than the normal people (8 cases volunteers) (P<0.05). It pointed out that the sFas can conjugate with FasL competited with cellular membremous Fas and restrain the apoptosis of the tumor cell. The sFasL may cause other immunocytes which express Fas apoptosis by tranmechanism, which result in tumor cell evading immune attack.Collectively, our findings that higher FasL expression rate was observed in 8 cases lung adenocarcinoma cells and A549 cells, sFas and sFasL was evidently higher in patients with lung carcinoma than the normal people, and lung adenocarcinoma cells and A549 cells all can attack TILs though it can be blocked by anti-FasL body. These demonstrate FasL-Fas system is an important pathway of immune escape.
Keywords/Search Tags:NSCLC, lung adenocarcinoma, A549 cell line, TIL, FasL, sFas-sFasL, counterattack, immue escape
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