The Effects And Preliminary Mechannisms Of Cibsplatin, Gemcitabine, 5-FU Treatment On Mouse Second Lymphoid Organs And Homing Of T Cells

Objectives: Chemotherapy is one of the major treating methods for cancers. But due to its tolerance and non-specific property,the chemotherapy drugs cannot completely kill the tumor cells. Studies have shown that cancer patients generally show low immunity after undergoing chemotherapy. And nearly half of cancer patients died of infections before cancer invasion or organ failure. As we all know, the main anti-tumor immune cells are tumor antigen-specific T cells.These cells not only function as tumor killer,but also plays an important role in infection resist. As effective cells, na?ve T cells must migarated to the T-cells zone in the secondary lymphoid organs(SLOs) and interact with the antigen presenting cell like dendritic cells(DCs). The process that T cells and DCs chemoattracted to the specific T cell zone is also known as homing. Therefore, both the quality and quantity of T cells homing to SLOs determines the quality of the body’s immune response. To secret sufficient amount of chemokines to attract T cells homing to SLOs is a fundamental process for immune response. The fibroblastic reticular cells(FRCs),marked with gp38+CD31-, which is constitutively expresses CCL21、CCL19, and CCL21 was reported to play the most important role in chemoattracting T cells and dendritic cells(DCs). Previous studies have shown that decreasing the expression of chemokine can reduce the frequency of T cells and DCs encounter in T cell zones, thus weakening the strength of the immune response.Thus, We suppose that something is happen during the chemotherapy,such as secretion of CCL21、CCL19,the homing of T cells ? In preliminary experiments, we found that the homing of T cells to the T-cells zone had reduced accompany with CCL21 and CCL19 secreting reduced. We future selected three chemotherapy drugs which are commonly used in clinical treatment of lung cancer: cisplatin, gemcitabine, 5-FU. This study aims to demonstrate the affection and the prelimilary mechanism of CCL21 secreting and T cells homing in spleen during chemotherapy.Methods:1. Established mouse chemotherapy model, examined the homing of T cells by flow cytometry and immunofluorescence.2. Elisa and Immunofluorescence were used to measure the expression of CCL21、CCL19.3. The cultivation of spleen stromal cells coculture with the cisplatin, gemcitabine, 5-FU. Then detected the apoptosis of the stromal cells by flow cytometry, immunofluorescence, and also examind the expression of CCL21、CCL19 in mRNA level.Results:1. After the treatment with cisplatin, gemcitabine, 5-FU, T cells homing in mice spleen decreased, the secretary volumes of CCL21 downregulated.2. After the treatment with cisplatin, gemcitabine, 5-FU, the homing of T cells homing in mice and the volumes of CCL19 and CCL21 in lymph node have no change.3. Co-culture with cisplatin, gemcitabine, 5-FU lead the apoptosis of splenic stromal cells and the reduction of CCL21、CCL19.Conclusions:1. Treatment with cisplatin, gemcitabine, 5-FU can lead the reduction of CCL21 and decrease the T cells homing in the mice spleen,but not in the lymph node.2. The reason for decreased secretion of CCL21 and the less T cells homing in spleen is the apotosis of FRCs caused by cisplatin, gemcitabine, 5-FU treatment.