| BackgroundOral squamous cell carcinoma(OSCC)is the commonest malignant tumor in the mouth,and its cause has not been fully explored.Many studies have confirmed that the development of tumor has the close relationship with the immune system of the body.Dysfunction of T cells is a key mechanism of tumor escape and immune surveillance in tumor microenvironment.T cell dysfunction caused by abnormal expression of immune checkpoints is currently a research hotspot.Programmed death molecule-1(PD-1)/programmed cell death molecule ligand-1(PD-L1)and T cell immunoglobulin mucin molecule-3(TIM-3)are important immunomodulators that affect the function of T cells.In the tumor microenvironment,PD-1 is combined with its ligand PD-L1,which can inhibit the activity and function of T cells,inhibit the proliferation of T cells,and accelerate the apoptosis of T cells,so that T cells are either fatigue or incapacitated,by means of the SHP2/PI3K/Akt pathway,SKP2/P15/P27 pathway,Zap70/PKC/NF-?B pathway.TIM-3 is combined with the ligand galectin-9 and other proteins.By activating the STAT family signaling pathway,PI3K/Akt/mTOR pathway,and inhibiting the Akt/NF-kappa B signaling pathway,it achieves the synergistic effect with PD-1/PD-L1,contributing to the immune escape of tumor cells.Previous studies have found that PD-1 and TIM-3 are abnormal expression in various malignant tumors of the whole body,and are closely related to the development of the disease.Coexpression of PD-1 and TIM-3 exists in solid tumors such as colon cancer and liver cancer,which is closely related to the poor condition of patients.However,there are few OSCC related studies.Therefore,this paper intends to further study the role of PD-1/PD-L1 and TIM-3 in the development of OSCC.ObjectiveThis study was devised to check the expression of PD-1/PD-L1 and TIM-3 in OSCC tissues and normal oral mucosa.We analyze the role and clinical significance of PD-1/PD-L1 and TIM-3 in the development of OSCC,and investigate the pathogenesis of OSCC.And finally the results may provide a theoretical basis for the new immune targeted therapy of OSCC.MethodWe selected the research specimens collected from January 2016 to October2016 in henan province tumor hospital.We got 42 cases as the experimental group,which is archived by surgical resection and histopathologic diagnosis of OSCC.And we got 22 cases of normal oral mucosa tissues as control group,which were cut off because of the need by surgery.Application of immunohistochemistry and Real time Reverse Transcription-Polymerase Chain Reaction technology was to measure the protein and mRNA expression of PD-1/PD-L1,TIM-3 in OSCC and normal oral mucosa tissues.We made statistical analysis among the PD-1?PD-L1 and TIM-3 protein and the analyze relationship between the clinical pathologic features of patients with OSCC,and the correlation between indicators.Using SPSS 21.0 software for data statistics analysis.Qualitative data comparison between groups was compared with the?~2 test.Quantitative data were compared with t test.Spearman correlation analysis was used to analyze the correlation between target protein and mRNA.The test level is?=0.05 and P<0.05 is statistically significant.Result1.The expression of PD-1/PD-L1 and TIM-3 protein was significantly different in the experimental group and the control group.PD-1 protein in the group of OSCC and normal oral mucosa positive expression rate of 61.9%and 22.7%respectively,PD-L1 protein expressed in OSCC and normal oral mucosa group positive rate were66.7%and 4.5%respectively,TIM-3 protein in the group of OSCC and normal oral mucosa positive expression rate were 64.3%and 18.1%respectively,with significant statistical differences(P<0.05).2.The expression of PD-1/PD-L1 and TIM-3 mRNA was significantly different in the experimental group and the control group.PD-1 mRNA in OSCC and normal oral mucosa group the relative expression quantity were 0.257±0.253 and 0.002±0.000,PD-L1 mRNA in OSCC and normal oral mucosa group relative expression were 6.736±263.384 and 0.404±1.057,TIM-3 mRNA in OSCC and normal oral mucosa group relative expression were 13.041±2597.003 and 0.067±0.014,all have significant difference(P<0.05).3.The expression of PD-1/PD-L1 protein can be correlated with the patient's clinicopathological parameters.PD-1 protein in TNM staging?+?and?+?positive rate were 60.0%and 94.1%respectively,the difference is statistically significant(?~2=6.093,P=0.014).The positive expression rate of PD-L1 protein in patients with tumor size of?5.4cm and>5.4cm was 58.1%and 90.9%respectively,and the difference was statistically significant(?~2=3.941,P=0.047).There was no obvious correlation between TIM-3 protein expression and the clinical features of patients,with no statistical difference(P>0.05).4.PD-1 and TIM-3 expression have a correlation.Spearman correlation analysis found positive correlation between PD-1 and TIM-3 mRNA in OSCC tissues(rs=0.941,P=0.005).There was no significant correlation between PD-1 and PD-L1protein,PD-1 and TIM-3 protein,PD-L1 and TIM-3 protein(P>0.05).There was no significant correlation between PD-1 and PD-L1 mRNA,PD-L1 and TIM-3 mRNA(P>0.05).Conclusion1.The expression of PD-1/PD-L1 and Tim-3 in OSCC tissues were increased than normal oral mucosa tissues,which suggests that the function of T cells in the OSCC was in a state of inhibition,and that microenvironment of OSCC presents an immunosuppressive state.2.The expression of PD-1 in OSCC was correlated with TNM stage.The expression of PD-L1 in OSCC were related to the size of the tumor.But the expression of TIM-3 in OSCC was not significantly correlated with clinical parameters.The results suggest that the expression of PD-1/PD-L1 was related to the severity and prognosis of the patients'clinical OSCC.3.In OSCC,the expression of PD-1 and TIM-3 mRNA are positively correlated,prompting that PD-1 and TIM-3 played a synergistic role in OSCC tissues,and PD-1and TIM-3 may co expressed.4.PD-1/PD-L1 and TIM-3 might be the biological markers of OSCC,and the targets for the immunotherapy of OSCC... |
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