| Background and objectiveOral squamous cell carcinoma(OSCC)is the most common type of disease in oral and maxillofacial malignancies,and its incidence tends to increase year by year.Due to the suppression of immune function and the immune escape mechanism of tumor,the treatment of OSCC failure.T cells play an important role in the immune system.When exposed to tumor antigens for a long time,T cells will express abnormal co-inhibitory molecules,leading to T cell dysfunction.PD-1 and TIM-3 are important negative regulatory factors in the coordination of the stimulation molecule family and play an important role in tumor immunity.Previous studies have shown that PD-1 and TIM-3 are abnormally expressed in liver cancer,non-small cell lung cancer and other malignant tumors,and their expression levels are closely related to the occurrence and development of tumors.In recent years,PD-1/PD-L1 monoclonal antibody therapy has made breakthrough in tumor treatment,and PD-1 antibody Pembrolizumab,PD-L1 antibody Durvalumb and other first-line drugs have been approved by the USA food and drug administration(FDA)for the treatment of advanced tumors.TIM-3 antibody has a good curative effect in laboratory studies of multiple tumors,and the combined application of PD-1 and TIM-3 antibody can achieve better therapeutic effect,and TIM-3 is expected to become a new target of cancer immunotherapy.Although studies have shown that PD-1/PD-L1 is involved in the immune escape mechanism of OSCC,the mechanism of TIM-3 in OSCC remains to be studied.In this paper,we studied the expression of PD-1,TIM-3 in oral squamous cell carcinoma tissues and peripheral blood T cells,and analyzed the relationship between two indicators and clinicopathological characteristics of patients with OSCC.The correlation between PD-1 and TIM-3 was analyzed and the pathogenic mechanism of OSCC was explored further,to provide a theoretical basis for the immunotherapy of OSCC.Methods1.In this experiment,60 cases of paraffin-embedded tissue(FFPE)(40 cases of OSCC and 20 cases of normal oral mucosa)were collected from the department zof pathology in the first affiliated hospital of Zhengzhou university and the affiliated tumor hospital of Zhengzhou university.The method of immunohistochemistry was used to detect the expression of PD-1,TIM-3 from protein levels in OSCC and normal tissues.We analyzed the correlation between each indicator and clinicopathological characteristics and their relationship.2.Peripheral blood samples of 40 patients with OSCC were collected before surgery or treatment,and the samples of 20 healthy subjects were collected.The expression of PD-1 and TIM-3 on T cells were detected by flow cytometry.We analyzed the correlation between each indicator and clinicopathological characteristics and their relationship.3.Using SPSS 21.0 software for data statistics analysis.Theχ~2 test was used for the comparison between groups of qualitative data.The t test was used for the comparison between groups of quantitative data.Spearman correlation analysis was used for the correlation analysis.P<0.05 was considered statistically significant.Results1.The expression of PD-1 and TIM-3 proteins were significantly different between the OSCC group and the normal oral mucosa group.The positive expression rates of PD-1 in the OSCC group and the normal oral mucosa group were 60.0%and20.0%.The positive expression rates of TIM-3 protein in the OSCC group and the normal oral mucosa group were 62.5%and 20.0%,and the differences were statistically significant(P=0.003,P=0.003).2.The relationship between the expression levels of PD-1 and TIM-3 proteins and the clinicopathological characteristics of OSCC patients.The positive rates of PD-1 protein in lymph node metastasis(85.7%)was higher than that in without lymph node metastasis group(46.1%),and the difference was statistically significant(χ~2=5.934,P=0.015);The positive rates of TIM-3 protein in stage I+II and III+IV in TNM stage were 50.0%and 81.3%,respectively,and the difference was statistically significant(χ~2=4.000,P=0.046).3.The expression of PD-1 and TIM-3 on CD4~+T cells in peripheral blood of patients with OSCC were significantly higher than that of healthy subjects(10.573±3.090%VS 4.335±1.091%,11.430±3.442%VS 4.710±1.018%,P<0.05),and the expression of PD-1 and TIM-3 on CD8~+T cells in peripheral blood of patients with OSCC were significantly higher than that of healthy subjects(4.045±1.227%VS0.875±0.412%,4.213±1.273%VS 1.195±0.632%,P<0.05).4.The expression of PD-1 and TIM-3 on CD4~+T or CD8~+T cells in peripheral blood and the clinical pathological characteristics of OSCC patients.We found PD-1and TIM-3 on CD4~+T cell were not statistically significant with age,gender,location,tumor size and other clinicopathological characteristics(P>0.05).The expression of PD-1 on CD8~+T cells was related to the lymph node metastasis(t=-2.343,P=0.024);the expression of TIM-3 on CD8~+T cells was correlated with the lymph node metastasis(t=-2.087,P=0.044).5.There was a positive correlation between the expression of PD-1 and TIM-3.Spearman correlation analysis found that there was a positive correlation between PD-1 and TIM-3 protein expression(rs=0.354,P=0.027).And there was a positive correlation between the expression of PD-1 and TIM-3 on CD4~+T or CD8~+T cell in the peripheral blood of OSCC patients(r_s=0.686,P<0.001;r_s=0.609,P=0.001).Conclusions1.The expression levels of PD-1 and TIM-3 in oral squamous cell carcinoma tissues were higher than those in normal tissues,suggesting that the local T cell immune function of OSCC is inhibited,and that microenvironment of OSCC presents an immunosuppressive state.2.The expression of PD-1 and TIM-3 on CD4~+T or CD8~+T in the peripheral blood of patients with OSCC was significantly higher than those of the healthy control group,suggesting that the immune function of peripheral T cells in patients with OSCC is inhibited.3.In oral squamous cell carcinoma tissues,the expression level of PD-1 protein was correlated with lymph node metastasis,and the expression level of TIM-3 protein was correlated with TNM stage.In the peripheral blood of patients with OSCC,the expression level of PD-1 on CD8~+T cells was correlated with lymph node metastasis,and the expression level of TIM-3 on CD8~+T cells was also correlated with lymph node metastasis.Which suggest PD-1 and TIM-3 may play an important role in the development of OSCC.4.In OSCC patients,the expression levels of PD-1 and TIM-3 were positively correlated in both oral squamous cell carcinoma tissues and peripheral blood,suggesting that PD-1 and TIM-3 may have co-expression and synergistic effects.5.TIM-3 may be a new tumor molecular marker and immunotherapy target for OSCC. |
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