Effects Of Neoadjuvant Chemotherapy On The Expression Of Programmed Death Ligand-1 And Tumor Infiltrating Lymphocytes In Lung Cancer Tissues

Background and Objective: At present,immunotherapy has been developed in many fields of tumor treatment,which can improve anti-tumor immune effects by stimulating the body’s immune system.Immune checkpoints programmed death 1(PD-1)and its ligand programmed death ligand 1,2(PD-L1,PD-L2)pathways can mediate negative synergistic stimulation signals,inhibit T cell function.It plays an important role in the participation of tumor immune escape and the formation of tumor microenvironment.At present,immunotherapy combined with chemotherapy can increase the objective response rate of cancer patients,but the mechanism of combination therapy is not yet clear.This study aims to analyze the changes of PD-L1,PD-L2 on lung cancer tissues and the changes of TILs(CD4+,CD8+,CD28+,and CD56+ lymphocytes)surrounding the tumor before and after neoadjuvant chemotherapy(platinum-based),in order to provide a theoretical basis for relevant clinical studies.Patients and Methods: In this study,tumor samples were obtained from 26 patients who confirmed primary lung cancer prior to and after NAC from January,2009 to October,2016 in the First Hospital of Jilin University.Of 26 patients,the expression of PD-L1,PD-L2 in lung cancer specimens was assessed by IHC.5%,10%,20%,30%,50% expression thresholds were used to define PD-L1,PD-L2 positive status,respectively.Of 16 patients(since the biopsy tissue specimens were limited,only 16 cases of biopsy and postoperative tissue specimens were collected),the expression of TILs(CD4+,CD8+,CD28+,and CD56+ lymphocytes)around the tumor before and after NAC were assessed by IHC.SPSS 19.0 software was used to analyze the data: The changes of PD-L1 and PD-L2 in lung cancer tissues before and after NAC were assessed by paired chi-square test.The changes of TILs(CD4+,CD8+,CD28+,and CD56+ lymphocytes)around the tumor before and after NAC were assessed using the paired T-test.Spearman’s rank correlation analysis was used to evaluate the correlation between the changes of PD-L1 in lung cancer tissues and tumor shrink rate and the interval from the end of NAC to operation.Non-parametric tests were used to evaluate the relationship between the changes of PD-L1 in lung cancer tissues and pathological type,gender and smoking status.P<0.05 was considered statistically significant.Results: 1.Of 26 patients,when using 5%,10%,and 20% as expression threshold to define PD-L1 positive status,65.4%(17/26),53.8%(14/26),and 42.3%(11/26)were found to be PD-L1 positive prior to NAC,and 92.3%(24/26),80.8%(21/26),69.2%(18/26)expressed positively after NAC,PD-L1 was up-regulated after NAC(P=0.008,P=0.016,P=0.016),however,there were no obviously statistical significance about the expression of PD-L1(P>0.05)when using 30%,50% expression threshold.2.Of 26 patients,the expression of PD-L2 were not show any statistical significance before and after NAC(p>0.05).3.Of 16 patients,the expression of CD4+,CD8+,and CD28+ lymphocytes increased after NAC compared with that before NAC(P=0.014,P=0.038,P=0.021),whereas the change of CD56+ lymphocytes was not statistical significant(P> 0.05).4.Of 26 patients,there were no significant difference between the changes of PD-L1 and tumor shrink rate,interval from the end of NAC to operation,pathological type,gender and smoking status(P>0.05).Conclusions: 1.The expression of PD-L1 in lung cancer tissues were increased after NAC when the expression thresholds are 5%,10%,and 20%.2.The expression of CD4+,CD8+ and CD28+ lymphocytes were increased after NAC.3.No correlation exists between the variation of PD-L1 and tumor shrink rate,interval from the end of NAC to operation,pathological type,gender and smoking status.