The Applied Study On Specific Immunotherapy Of Dendritic Cells In Cervical Cancer

Background : Cervical cancer is gynecological tumor of upper deathrate. Surgery and radiotherapy is the major treatment, chemotherapy is theassisted treatment. But the traditional treatment failed to obviously improvesurvival rate of 5 years in advance stage patient and hyposensitivity forradiotherapy with chemotherapy. Therefore, it is quite necessary toimprove effect and survival rate of cervical cancer that exploringcomprehensive therapy measures comprising immunotherapy. Dendriticcells (DCs) are the most important and professional antigen-presentingcells in vivo, which have unique immune function. DCs are able to presenttumor antigen to T cells efficiently and initiate anti-tumor immuneresponses. This study aimed at comprehensive therapy of cervical cancerand suggested the treatment of low-dose chemotherapy combined withimmunotherapy of dendritic cells inducing. To observed the effect in thetransplantation model of mice cervical cancer and evaluated feasibility ofclinical application. Thereby, it can provide theoretic and experimentalbasis for clinical comprehensive treatment of cervical cancer. Objective : To establish a method of expanding immature dendriticcells from bone marrow of BALB/c mice bearing mice's cervix carcinomacell line No. 14 (U14) cervical cancer in vitro. To investigate the antitumorimmune response to mice cervical cancer of low-dose chemotherapycombined with immunotherapy of dendritic cells inducing. Methods : ①To establish transplantation models of mice bearingU14 cervical cancer ( tumor-bearing mice ). Tumor sizes were observedeveryday. ②The cells isolated from bone marrow of tumor-bearing micewere cultured in medium with granulocyte-macrophage colony stimulatingfactor (GM-CSF) and interleukin 4 (IL-4). Morphological change wasobserved by inverted microscope everyday and electron microscope after5days and 7days' culture. ③The tumor-bearing mice was treated with 3doses of intraperitoneal chemotherapy. Then to evaluate effect ofchemotherapy and confirm only dose. ④ To evaluate effect of fourtreatments of tumor-bearing mice. Thirty two tumor-bearing mice wererandomly divided into 4 groups : group A(control group), groupB(low-dose intraperitoneal chemotherapy group), group C(immunotherapygroup of immature DCs), group D(combined treatment group of low-doseintraperitoneal chemotherapy plus immunotherapy of immature DCs). Allgroup mice were killed in the 15th days. To compare the mean survivaltime of all group, to measure the tumor size and weight and count thetumor growth inhibitory rate, to detect the U14 cell apoptosis rate withFCM. Results : ①The successful tumor transplantation was obviouslyobserved after 4 days of bearing U14 in all group. The mean diameter oftumor was ≥ 5mm and the tumor was obviously touched by hands. ②Alarge number of morphological typical immature DCs were observed afterthe culturing of tumor-bearing mice bone marrow cells for 7 days. ③Therewas a significant difference in the tumor size and weigh of group Ⅲ andⅠ(P<0.05). There was very remarkable difference in the tumor size andweigh of group Ⅳ and Ⅰ(P<0.01). ④The mean survical time in 4groups tumor-bearing mice have not significant difference(P>0.05). Therewas a very significant difference in the tumor size and weigh and U14 cellapoptosis rate of group D compared with group A,B,C(P<0.01). Thetumor growth inhibitory rate and U14 cell apoptosis rate of group D was10.45% and 11.26% respectively, it was the highest. In the tumor size andweigh and U14 apoptosis rate, there was no marked difference in both sidesof group C(P>0.05), while there was a significant difference in both sidesof group D(P<0.01). Conclusions : ①The transplantation model of mice bearing U14cervical cancer was successfully established. ② A large number ofmorphological typical immature DCs can be generated by in vitro cultureof tumor-bearing mice bone marrow cells. ③The only intraperitonealchemotherapy dose before immunotherapy of immature Im DCs was 5-Fu15 mg/kg · d and DDP 1mg/kg · d respectively. ④ The low-dosechemotherapy...