Relationship Between Tumor-associated Autoantibodies And Immunotherapy Prognosis In Patients With Advanced NSCLC

BackgroundImmune checkpoint inhibitors have become an important method for the treatment of lung cancer,and it is widely used,but the therapeutic effect is difficult to predict.Evidence-based medical evidence believes that when the PD-L1 expression of NSCLC patients’ pathological tissues is>=1%,the use of PD-1/PD-L1 inhibitors will benefit the patients,but in clinical practice,sufficient pathological tissues are often not available,and therapeutic effect of the treatment is also very different.Immunotherapy improves the killing effect on tumor cells by enhancing cellular immune function.irAE is caused by immune enhancement-Once a serious irAE occurs,it will not only interfere with normal treatment decisions,but also bring significant risks to patients with advanced NSCLC.On the other hand,the existing immunotherapy is mainly to activate/enhance the cellular immune function of T cells,and the role of humoral immunity in the development and treatment of lung cancer has not been fully studied.PurposesTo study the relationship between the expression level of tumor-associated autoantibodies(TAAbs)and the survival,response and occurrence of irAE in patients with NSCLC after immunotherapy,and to find potential biomarkers.MethodsThe subjects of the study were 132 patients who received immunotherapy in the Department of Respiratory Medicine of Peking Union Medical College Hospital due to inoperable stage Ⅲ or Ⅳ non-small cell lung cancer from July 2017 to September 2020.Collect clinical data of these patients,including peripheral blood to test 37 kinds of tumor-associated antigen autoantibodies before immunotherapy(22 autoantibodies are brand-new and have never been reported and analyzed in the literature),patients’medical history,clinical stage,pathological tissue classification,immunotherapy effect,progress free survival(PFS),occurrence of irAE.According to whether the autoantibodies of 37 tumor-associated antigens tested are positive(detected by ELISA method),the relationship between one or several combinations of autoantibodies and the patients’PFS,response and irAE after immunotherapy is found through statistical methods.Results1.The 99 patients were randomly divided into training cohort/validation cohort.Chi-square test and regression analysis proved that the BRCA2 ZNF768 PARP MAGEA4 autoantibody combination is an independent predictor of whether irAE will occur after immunotherapy in patients with advanced NSCLC(p=0.038,HR=5.812).2.Use Kaplan-Meier curve and Cox regression on the training cohort/validation cohort to prove that the P53 CAGE MAGEA4 GAGE7 UTP14A IMP2 PSMC1 autoantibody combination is an independent predictor of immunotherapy pfs for patients with advanced NSCLC(p=0.028 HR=0.417).Conclusions1.The risk of irAE after receiving immunotherapy in advanced NSCLC patients who have positive BRCA2 ZNF768 PARP MAGEA4 autoantibody panel is 5.812 times that of the patients with the negative panel.2.The risk of disease progression after receiving immunotherapy in advanced NSCLC patients who have positive P53 CAGE MAGEA4 GAGE7 UTP14A IMP2 PSMC1 autoantibody panel is 0.417 times that of the patients with the negative panel.3.The expression of TAAbs in peripheral blood can be used as a predictor and biomarker of the effect of immunotherapy and the occurrence of irAE in patients with advanced NSCLC.