Relationship Between TIGIT/PD-1 Level And Clinicopathologic Features In Patients With Non-small Cell Lung Cancer

Background and objectives:Lung cancer is a malignant tumor with high morbidity and mortality worldwide.In recent years,therapies for non-small cell lung cancer(NSCLC)have developed rapidly,and immunotherapy in particular has brought lasting benefits to patients with advanced NSCLC.The emergence of numerous immune checkpoint inhibitors(ICIs)has ushered in a new era of NSCLC treatment.For example,the application of programmed death receptor-1 / programmed death ligand 1(PD-1/PD-L1)inhibitors in patients with advanced lung cancer can extend progression-free survival(PFS)and overall survival(OS),providing a new therapeutic direction for non-small cell lung cancer patients without gene mutations.However,some patients do not benefit from it,so exploring new immunotherapeutic targets remains the focus of current research.T cell immunoglobulins and immunoreceptor tyrosine inhibitory motif domains(TIGIT)are immune checkpoint molecules that negatively regulate NK(NK)cells and T cells.The present results show that in the CITYSCAPE phase II study,TIGIT inhibitor combined with PD-L1 inhibitor has shown good anti-tumor effect in patients with advanced NSCLC,but in the SKYSCRAPER-01 Phase III clinical study,the therapeutic effect in patients with highly expressed PD-L1 has not met clinical expectations.As far as the current research results are concerned,the definition of the beneficiaries of PD-1/PD-L1 inhibitors and TIGIT inhibitors is still an unsolved problem.The objective of this study was to analyze the expression of immune checkpoint TIGIT and PD-1 in tumor tissues and peripheral blood of patients with NSCLC.To investigate the relationship between TIGIT/PD-1 level and clinicopathologic features and prognosis.In order to provide theoretical basis and preliminary clinical observational results for the precision of NSCLC immunotherapy.Methods:1.Cancer and paracancer tissues of 64 patients with NSCLC who underwent surgical treatment in the Department of Thoracic Surgery,Affiliated Hospital of Qingdao University from January,2019 to December,2019 were collected,and the results were confirmed by histopathology.TIGIT,PD-1 and CD155 were stained by immunohistochemical method(IHC).The expression levels of TIGIT,PD-1 and CD155 in tissues of NSCLC patients were determined,and the relationship between immunohistochemical scores and clinicopathological features was analyzed.2.The relationship between the expression levels of TIGIT,CD155 and PD-1 genes and the survival prognosis of NSCLC patients was analyzed by searching the GEPIA database.3.Peripheral blood of 15 patients with NSCLC and 11 healthy subjects diagnosed in the Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Qingdao University from February,2022 to February,2023 were collected.TIGIT and PD-1expression on peripheral blood T cells were detected by flow cytometry.The differences in the distribution of T cell subtypes in peripheral blood of different pathological types of NSCLC and the differences in the expression of TIGIT and PD-1 in peripheral blood T cells of NSCLC patients and healthy controls were compared,and the relationship between the expression levels of TIGIT and PD-1 in peripheral blood T cells of NSCLC patients and clinicopathologic features was analyzed.SPSS 27.0 statistical software and Graph Pad Prism 8 software were used for data analysis.Results:1.Immunohistochemical results showed that the expression of TIGIT and PD-1 in cancer tissues of NSCLC patients was significantly higher than that in paracancer tissues,with statistical significance(P < 0.001);The expression levels of TIGIT,CD155 and PD-1in cancer tissues were related to the degree of tumor differentiation and clinical stage.The positive expression rates of TIGIT,CD155 and PD-1 were higher in patients with lower degree of tumor differentiation and later clinical stage,and the difference was statistically significant(P < 0.05).In addition,our results also showed that TIGIT expression level was higher in patients with lymph node metastasis,and PD-1 expression level was higher in patients with squamous cell carcinoma compared with adenocarcinoma,with statistical significance(P < 0.05).The expression levels of TIGIT,CD155 and PD-1 were not correlated with gender,age,smoking history,primary tumor site,tumor size,pleural invasion or gene mutation(P > 0.05).2.TIGIT was positively correlated with PD-1 expression(r=0.302,P < 0.05),and CD155 was positively correlated with PD-1 expression(r=0.269,P < 0.05).3.The survival time of TIGIT and PD-1 high expression group was shorter than that of low expression group,but the difference was not statistically significant(P > 0.05);The survival time of high CD155 expression group was shorter than that of low CD155 expression group,and the difference was statistically significant(P < 0.05).4.Flow cytometry showed that the proportion of CD4+T lymphocytes in CD3+T cells was higher than that in CD8+T cells in healthy control group,the difference was statistically significant(P < 0.01).In squamous cell carcinoma patients,the proportion of CD4+T lymphocytes was similar to that of CD8+T lymphocytes,but the difference was not statistically significant(P > 0.05).In adenocarcinoma patients,CD4+T lymphocytes accounted for a higher proportion than CD8+T lymphocytes,and the difference was statistically significant(P < 0.05).The T cell expression of CD4+TIGIT+,CD4+PD-1+,CD8+TIGIT+,CD8+PD-1+ in lung cancer group was significantly higher than that in healthy control group,the difference was statistically significant(P < 0.05).The expression level of TIGIT on CD8+T cells in peripheral blood was related to the pathological type of tumor.Patients with adenocarcinoma expressed higher levels of TIGIT on peripheral blood CD8+T cells than patients with squamous cell carcinoma,and the difference was statistically significant(P < 0.05).Conclusion:1.TIGIT and PD-1 play a certain role in promoting the occurrence and development of non-small cell lung cancer.2.The expression of TIGIT in cancer tissues is related to the degree of tumor differentiation,clinical stage and lymph node metastasis.The lower the degree of differentiation,the later the stage and lymph node metastasis,the higher the expression level of TIGIT.3.High expression of TIGIT is a risk factor for poor prognosis in NSCLC patients.