Tumor-associated Autoantibodies In Patients With Advanced NSCLC Studies On The Correlation Of Immune Efficacy

Objective:The aim of this study was to investigate the association between peripheral blood tumor-associated autoantibodies(TAAb)and the efficacy of immunocheckpoint inhibitors(ICIs)in advanced non-small cell lung cancer(NSCLC).Methods:The study subjects were 50 patients diagnosed with stage IIIB-IV non-small cell lung cancer who received first-line/second-line ICIs-based monotherapy or combination chemotherapy during 2021-2022 in the Department of Oncology of our hospital.Clinical data of each patient were recorded.Such as age,gender,smoking status,pathological type,clinical stage and ECOG score,fresh venous blood was collected from each patient within 7 days prior to initial immunotherapy administration.The expression levels of TAAb(TRIM21,BRCA2,TXNDC2,P53,IMP2 and MAGEA4)in peripheral blood of the patients were detected by enzyme-linked immunosorbent assay(ELISA).Meanwhile,the efficacy of each patient receiving immunosuppressant was observed,and the efficacy of RECIST1.1 was evaluated.The patients were divided into progressive group and non-progressive group according to their survival.The main endpoint of observation were objective response rate(ORR),disease control rate(DCR)and progression-free survival(PFS).SPSS 26.0 software was used for statistical analysis,and binary multinomial Logistic regression was used to analyze the independent influencing factors of disease progression.Critical values of relevant antibody indicators were calculated by receiver operating curve(ROC)curve analysis,survival analysis was performed using Kaplan-Meier method,comparison of differences between groups was performed using Log-rank test,and multivariate analysis of influencing disease progression was performed using COX regression model.In Log-rank test,P < 0.1was considered statistically significant,and other results were P< 0.05 was considered statistically significant.Results:The enrolled patients were divided into progressive group and non-progressive group according to their survival conditions.According to the rank sum test,the expression levels of autoantibodies of IMP2,TXNDC2 and P53 antigens may be correlated with the progression of the disease(P < 0.05),which were included in the multivariate analysis.Logistic regression results showed that higher IMP2 and P53 antigen autoantibody expression levels were independent factors affecting the disease progression of patients,and the OR values were0.942 and 0.997,respectively.The critical values of IMP2 and P53 antibody expression levels to predict the disease progression of patients were determined by ROC curve analysis.Were2.7(Se 0.81,Sp 0.552,AUC 0.709)and 4.8(Se 0.667,Sp 0.69,AUC 0.67),respectively.IMP2 and P53 were combined into a TAAb group.When the antibody expression level was greater than the critical value,it was positive;when the antibody expression level was less than the critical value,it was negative.If either of the autoantibodies in IMP2 and P53 were positive,the TAAb combination was considered positive;if both were negative,the TAAb combination was considered negative.Finally,the enrolled patients were divided into 36 positive cases and 14 negative cases.The results of survival analysis by Kaplan-Meier method were as follows: The median PFS of TAAbs positive group and TAAbs negative group were318 days and 228 days,respectively(P=0.008),and the DCR of positive group was higher than that of negative group(22.2% vs.14.3%),and the difference was statistically significant(P < 0.05).In order to further explore the effects of IMP2 and P53 antibody expression levels on PFS,single-factor Log-rank test results suggested: IMP2 and P53 antibody expression levels may be correlated with patients’ PFS(P < 0.10).Cox multivariate survival analysis suggested that P53 antibody expression level was an independent predictor of PFS in patients with advanced NSCLC treated with ICIs(P < 0.05).Conclusion:The expression level of TXNDC2 antibody may be correlated with disease progression in patients with advanced NSCLC after ICIs treatment.Higher IMP2 and P53 autoantibody expression levels are independent predictors of disease progression and may be associated with longer PFS.A positive TAAb combination may be associated with better outcomes and longer PFS in patients with advanced NSCLC treated with ICIs.