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Efficacy And Mechanism Of Thermal Ablation Combined With Adoptive Cellular Immunotherapy For Malignant Tumors

Posted on:2022-01-13Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y F LiFull Text:PDF
GTID:1484306350497184Subject:Medical imaging and nuclear medicine
Abstract/Summary:PDF Full Text Request
Purpose:To evaluate the effect of thermal ablation combined with activated functional killer(AFK)cells immunotherapy for patients with malignant tumors.Methods:A cohort of 10 patients with malignancies received thermal ablation combined with AFK cells immunotherapy was retrospectively analysed.Progression-free survival(PFS),overall survival(OS),laboratory test,and postoperative complications were assessed.Results:There were no severe complications and no liver or kidney damage after therapy.The median PFS was 12 months(0-25 months).Compared with pre-ablation,hemoglobin(P=0.023),hematocrit(P=0.034)and lymphocyte ratio(P=0.023)were significantly reduced after ablation.Neutrophil-to-lymphocyte ratio(NLR p=0.038),neutrophil ratio(p=0.016),albumin(p=0.006),alkaline phosphatase(p=0.029),CA-125(p=0.033)and D-dimer(p=0.011)were significantly increased.The leukocytes(P=0.003),neutrophils(P=0.024)and lymphocytes(P=0.003)were significantly increased,and the ratio of monocytes(P=0.008)and eosinophils(P=0.005)were significantly decreased after treatment,while there were no significant differences in other indicators.Patients who survived at the end of follow-up experienced a significant increasing in lymphocytes after treatment(P=0.001),After combination treatment,the percentages of CD3+cells(P=0.016)and CD3+CD8+cells(P=0.002)increased,while the percentages of CD3-CD16+CD56+(P=0.002)and CD4+/CD8+(P=0.016)decreased.Conclusion:Combination of thermal ablation and activated functional killer cells immunotherapy is a safe and effective method for the treatment of malignant tumors.And adoptive immunotherapy with AFK cells may be helpful to prevent recurrence after thermal ablation in selected patients with advanced cancer.Purpose:To investigate the feasibility and safety of microwave ablation combined with activated functional killer cells(AFK)immunotherapy for advanced NSCLC.Methods:Six patients with advanced NSCLC who were enrolled for microwave ablation combined with AFK immunotherapy were initially evaluated,including laboratory examination,postoperative complications,and the local status of treated tumor.Results:There were no serious complications after combined therapy.There was no significant difference in blood routine,liver and kidney function,blood coagulation function and tumor markers after combined treatment.After combination therapy,the proportion of total T cells,killer T cells,NK cells and NKT cells were significantly higher than that before treatment(P<0.05),and the proportion of helper T cells was lower than that before treatment(P>0.05).Conclusion:Microwave ablation combined with AFK immunotherapy of advanced NSCLC is a safe and local effective method.Purpose:To investigate the effectiveness and immunological changes of microwave ablation therapy combined with AFK cell immunotherapy on distant tumors of lung cancer in mice.Methods:Based on the subcutaneous tumor model of lung cancer in B-NDG mice,the distant tumor model was established and two experiments were carried out,including microwave ablation combined with AFK cell immunotherapy vs.microwave ablation alone and microwave ablation combined with AFK cell immunotherapy vs.surgical resection combined with AFK cellular immunotherapy.The growth of mice and tumor were observed,the body weight and tumor size of mice were recorded,and the proportion and activity of AFK cells infused in peripheral blood of mice were detected.At the end of the experiment,AFK cells in tumor were detected,and pathological examination was performed.Results:MWA+AFK group had a longer,and the tumor growth rate was slower than that of the single ablation group.Compared with the single ablation group,the tumor inhibition rate of the combined treatment group was 57.3%.The number of AFK cells in the combined treatment group was higher than that of the AFK group.CD4+and CD8+T cells were depleted obviously after infusion,and the activation level of T cells was higher than that of the AFK group.The CD8+ cells in tumor tissues,spleen and peripheral blood were nearly exhausted in the combined treatment group,while the proliferation ability of tumor cells was significantly lower than that in single ablation group.The tumor growth rate in the MWA+AFK group was slower than that in the OP+AFK group.Compared with the OP+AFK group,the tumor inhibition rate in the MWA+AFK group was 28.5%.T cell activation level in MWA+AFK group was higher than that in OP+AFK group.Conclusion:microwave ablation combined with AFK cell immunotherapy can not only eliminate the primary tumor of lung cancer,but also inhibit the growth of distant tumor.Microwave ablation can activate transfused AFK cells.Purpose:To investigate the differential serum protein expression in mice after ablation of lung cancer by iTRAQ,while to explore the mechanism of activation of exogenous immune cells after ablation and the mechanism of action on tumor.Methods:Nine female 5-week-old SPF B-NDG mice were selected to establish the subcutaneous tumor model of lung cancer.The peripheral plasma was collected before and after microwave ablation,while the proteins were extracted and detected by protein spectrum with iTRAQ technology.The proteomic differences between before and after ablation was analyzed by screening differential proteins,GO enrichment,KEGG signal pathway enrichment and other bioinformatics methods.Results:A variety of protein fragments released after microwave ablation as antigens activated exogenous immune cells.A total of 300 differentially expressed proteins were identified after ablation,including 90 human species and 210 mouse species,enriched in metabolism,death and tumor-related pathways.There were 18 human species key differential protein,including 7 up-regulated and 11 down-regulated proteins,and 29 mouse species,including 4 up-regulated and 25 down-regulated proteins.Conclusion:A variety of peptide released in blood after microwave ablation can act as antigens activated exogenous immune cells.Multiple signal pathways are activated after microwave ablation of lung cancer,which affect tumor proliferation,apoptosis,metastasis and signal transduction,or promote tumor progression,or accelerate tumor death.
Keywords/Search Tags:Malignant tumors, adoptive immunotherapy, microwave ablation, radiofrequency ablation, combination therapy, NSCLC, lung cancer, B-NDG, immunological effect, bioinformatics, differential protein
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