Clinical Significance Of Various Immunocheckpoint Expressions In Non-Small Cell Lung Carcinoma

Objective:To investigate the expression of Programmed cell death-ligand 1 (PD-L1), Programmed cell death-1 (PD-1), Lymphocyte activation gene-3 (LAG-3), B and T lymphocyte attenuator(BTLA), Cytotoxic T lymphocyte-associated antigen-4(CTLA-4) in NSCLC, analyze their relationship with the clinical pathologic characters and prognosis, and further explore the relationship between these immune checkpoint (PD-L1, PD-1, LAG-3, BTLA, CTLA-4). Methods:This study included 107 NSCLC patients, and they did not receive other systematic anti-tumor treatment before surgical treatment, including radiotherapy, chemotherapy and immunotherapy. Immunohistochemistry method was used to detect the expression of PD-Ll, PD-1, LAG-3, BTLA, CTLA-4 in 107 cases of NSCLC postoperative tumor tissue. All cases in this group were with complete follow-up data, the deadline for postoperative recurrence. We use the chi-square test to analyze their correlation with the clinical pathologic characters and correlation between various immune checkpoint, Kaplan-Meier Method to estimate the DFS, Cox regression model to analyze the independent factors influencing the prognosis of NSCLC. Results:1. The correlation of immune checkpoint with clinical pathologic characters:In this study, statistical data show that the positive expression rate of immune checkpoint (PD-L1, PD-1, LAG-3, BTLA, CTLA-4) were 43.9%(47/107),41.1%(44/107),43.9%(47/107),48.6%(52/107),52.3%(56/107) in 107 cases of tumor specimens, the others were negative or weakly positive. There are statistical correlation between the expression of PD-L1 and pathological type(P=0.007), lymph node metastasis(P=0.040) and Ki-67(P=0.007); the expression of PD-1 shows correlation with smoking(P=0.010);there are statistical correlation between the expression of LAG-3 and pTNM stage (P=0.001), lymph node metastasis(P=0.009); the expression of BTLA was correlated with gender(P=0.025), smoking(P=0.000); the same as the expression of PD-L1, Ki-67(P=0.022) has the correlation with CTLA-4, but it has no correlation with other clinical pathologic characters.2. The correlation of immune checkpoint with prognosis of seclected NSCLC patients:according to the Kaplan-Meier survial curve were showed, the status of PD-L1 and LAG-3 associated with prognosis in this group, PD-L1 positive subgroup has a shorter 3 years DFS than negative subgroup, but LAG-3 positive subgroup has a longer 3 years DFS. The results of cox regression model analysis show that pTNM stage and PD-L1 are the two independent risk factors to affect the DFS(P=0.000, P=0.013). On the contrary, LAG-3 is the independent protective factor for DFS(P=0.004).3. The correlation between PD-L1, PD-1, LAG-3, BTLA, CTLA-4:PD-L1 and CTLA-4 was negatively correlated(r=-0.211, P=0.029); CTLA-4 and LAG-3 was positively correlated(r=-0.241, P=0.012), and according to the Kaplan-Meier survial curve, this positive correlation exerted an positive influence on prognosis,which prompt that this subgroup patent has a longer DFS; in addition, CALA-4 and BTLA was positively correlated, but their correlation has no influence on prognosis; However, there are no significant correlation between other immune checkpoint(P>0.05). Conclusion:Immune checkpoint(PD-L1, PD-1, LAG-3, BTLA, CTLA-4) contribute to guide the evalution for prognosis, and there are some correlations between immune checkpoints that exerts an influence on prognosis.