Significance Of Soluble PD-L1,CTLA-4 And B7-H3 In Peripheral Blood In Healthy Patients And Patients With Lung Cancer Treated With PD-1 Inhibitors

Objective:To investigate the expression of soluble programmed death ligand(s PD-L1)soluble cytotoxic T lymphocyte associated antigen 4(sCTLA-4)soluble human B7 homologue 3(sB7-H3)in peripheral blood of patients with non-small cell lung cancer(NSCLC),and whether the expression of these factors can predict the efficacy of PD-1 inhibitors.Methods:(1)Patients with non-small cell lung cancer who were hospitalized in the Department of Oncology,Affiliated Hospital of Guilin Medical University from December 2019 to November 2020 were selected,inhibitor treatments for PD-1 single drug or combination therapy to collect patients clinical characteristics,and according to the review of imaging after treatment and other related information,evaluation of the patient’s disease control rates(DCR)objective response rate(ORR)and progression-free surial(PFS).(2)Fast-fasting blood samples were collected from all patients in the morning 1 week before medication,and 5ml was extracted with ordinary serum tube.After centrifugation at 1000 g for 15 minutes,the supernatant was taken and stored in-80 for later use.The contents of s PD-L1,sCTLA-4 and sB7-H3 in serum were determined by ELISA method.(3)Measurement data were expressed as mean standard deviation,while enumber data were expressed as case number and rate.Comparison between groups was performed by X~2test,Kaplan-Meier method to draw survival curves,and Log-rank test to compare the differences between survival curves.P<0.05 indicated statistically significant differences.Results:By January 31,2021,a total of 58 patients with advanced non-small cell lung cancer were collected,of which 5 patients were excluded because they did not return to the hospital for evaluation of efficacy,and a total of 53 patients were included in the study.The minimum age was 38 years old,the maximum was 80 years old,and the median age was 61 years old.There were 42 males and 11 females.There were 0 cases of CR(0%),21 cases of PR(39.6%),22 cases of SD(41.5%),and 10 cases of PD(18.9%)in the evaluable treatment.Disease control was achieved in 43 cases(81.1%),and objective remission was achieved in 21 cases(39.6%).The levels of s PD-L1 and SB7-H3in peripheral blood of lung cancer group were significantly higher than those of healthy control group,with statistical significance(P=0.0037,P=0.0025).Chi-square test showed that the expression of s PD-L1 and sCTLA-4 was closely correlated with smoking,distant metastasis and tumor stage(P<0.05).Chi-square test showed that there were statistically significant differences in DCR and ORR of peripheral blood s PD-L1 content among different expression levels(P<0.05).Kaplan-Meier method was used for survival analysis,and log-rank test was used to analyze the differences between groups.The expression level of peripheral blood s PD-L1 was grouped by the median value as the boundary,and the difference between the low value group and the high value group was statistically significant(X~2=11.069,P=0.001).Univariate analysis and Cox multivariate analysis showed that peripheral blood s PD-L1content was not only an influential factor for the prognosis of patients with lung cancer treated with PD-1 inhibitors,but also an independent risk factor(P=0.01).Conclusions:(1)Serum concentrations of s PD-L1 and SB7-H3 in lung cancer patients were significantly higher than those in healthy controls,suggesting that s PD-L1 and SB7-H3 may become new tumor markers.(2)The level of s PD-L1 was negatively correlated with the PFS of lung cancer patients treated with PD-1 inhibitors,and it was an independent risk factor.(3)SCTLA-4expression is associated with disease progression in patients treated with PD-1inhibitors.