Relationship Between Immune Checkpoint Expression And Pathological Features And Prognosis In The Immune Microenvironment Of Diffuse Large B-cell Lymphoma

Objective: Immune checkpoints are essential for maintaining autoimmune tolerance and inhibit the immune function of T cells.This study aims to analyze diffuse large B cell lymphoma(DLBCL),the expression of immune microenvironment of checkpoints,to explore its relationship with the clinical pathologic features and prognosis.Methods:174cases of DLBCL were collected from the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University.Immunohistochemical methods were used to detect the expression of PD-1,LAG-3,TIM-3 and TIGIT proteins at immune checkpoints in the patients.SPSS22.0 statistical software analyzed the experimental results:Chi-square test and rank sum test was used to analyze the correlation between immune checkpoint expression and clinicopathological features,Spearman correlation analysis was used to analyze the correlation between the expression of four immune checkpoints,Kaplan-Meier survival analysis and COX multivariate analysis of the impact of immune checkpoints on the prognosis of DLBCL patients.Results:In the tumor infiltrating lymphocytes(TILs),PD-1,LAG-3,TIM-3 and TIGIT the positive expression rate of79.3%,78.8%,62.7% and 69.5%,respectively.The positive expression of TIM-3 and TIGIT in tumor cells was 44.8% and 45.4%,respectively.TIM-3 expression in TILs was correlated with Ann-Arbor staging(P=0.039).PD-1 was positively correlated with LAG-3,TIM-3 was positively correlated with TIGIT,and univariate survival analysis showed that high expression of LAG-3 and PD-1/LAG-3 co-high expression in TILs were correlated with poor prognosis.Multivariate analysis showed that PS score and R-CHOP treatment were independent risk factors for survival in DLBCL patients.Conclusion: The expression level of TIM-3 is closely related to the Ann-Arbor stage,which is expected to be a new index for evaluating the aggressiveness of DLBCL.PD-1 is correlated with LAG-3 expression,and high expression of LAG-3 and PD-1/LAG-3 predicted poor prognosis of DLBCL.Therefore,LAG-3 may become a new target for immunotherapy,or be used in combination with PD-1 inhibitors to improve the current status of resistance in some DLBCL patients.