| BackgroundLung cancer is a kind of malignant tumors with the highest incidence and mortality in China,of which about 85%are non-small cell lung cancer(NSCLC).In 2013,"Breakthrough of the Year 2013" was published in the journal Science,and the cancer immunotherapy was on the top of the list.As a new treatment model,immunotherapy has become one of the hot spots in the field of cancer research.With the deepening of the research on the mechanism of tumor immune escape,we know that the programmed death factor 1(PD-1)and its ligand 1(programmed death ligand 1,PD-L1)can constitute a PD-1/PD-L1 molecular signaling pathways.Many studies have confirmed that PD-1/PD-L1 monoclonal antibody has a very good curative effect in the immunotherapy of various tumors by blocking the signaling pathways.But the low objective response rate of the medicine to solid tumor seriously restrict the immune targeted clinical treatment,it is urgent to study further on the mechanism of tumor immune to solve this problem.T cell immunoglobulin and mucin-domain-containing molecule 3(TIM-3)is another important negative costimulatory molecule,to which much attention has been paid in recent years.A lot of studies have shown that TIM-3 is involved in regulating immune suppression in the tumor microenvironment,and plays an important role in the development process.Objective1.Compare the efficacy and safety of Pembrolizumab with that of platinum-based double medicine in the PD-L1 positive advanced NSCLC patients.2.Explore the expression of PD-1,TIM-3 mRNA in T cells in peripheral blood of the PD-L1 positive advanced NSCLC patients before and after treatment with Pembrolizumab.MethodsA total of 18 PD-L1 positive advanced NSCLC patients were enrolled,of whom 5 were treated with Pembrolizumab as the experimental group,and 13 with carboplatin combined with paclitaxel as the control group.Compare the tumor lesions to evaluate the efficacy of the drug by imaging examination before the treatment and every 9 weeks after the treatment began.Quantitative RT-PCR was used to detect the expression of PD-1,TIM-3 mRNA in peripheral blood T cells of the patients in the experimental group before the treatment and every 3 weeks after treatment began.Then the indexes were statistically analyzed and charts were made.Results1.There were no statistically significance between the DCR,ORR,PFS of the PD-L1 positive advanced NSCLC patients treated by Pembrolizumab and that of the control group treated by platinum-based double medicinethe(P>0.05).But the incidence of gastrointestinal reaction in the experimental group was lower than that in the control groupand(P<0.05).So was the incidence of bone marrow depression(P<0.01).2.The difference of the relative expression of PD-1 mRNA in peripheral blood T cell in each patient or in each time point in experimental group was not statistically significant(P>0.05).The difference of the relative expression of TIM-3 mRNA in peripheral blood T cell in each patient was statistically significant(P<0.01),and that in each time point was not statistically significant(P>0.05).The difference between the relative expression of TIM-3 mRNA in peripheral blood T cell in the patient with ineffective drug therapy and that of other 4 patients was statistically significant(P<0.05).ConclusionThe DCR of Pembrolizumab in PD-L1 positive advanced NSCLC patients is the same with that of platinum-based double medicinethe,so were the ORR and the PFS.The incidence of gastrointestinal reaction and bone marrow depression of the experimental group were both lower than that of the control group,and the adverse reactions were mild.There was no significant difference in the relative expression of PD-1 mRNA in peripheral blood T lymphocytes before and after Pembrolizumab treatment,so was that in each patient.The high expression of TIM-3 mRNA may affect the treatment effect,is one of the mechanisms of resistance to Pembrolizumab. |
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