Peripheral Blood Autoantibodies Against to Tumor-Associated Antigen Predict Clinical Outcome to Immune Checkpoint Inhibitor-Based Treatment in Advanced Non-Small Cell Lung Cancer

Background Peripheral blood biomarkers to immunotherapy have attracted more and more attentions owing to noninvasive nature. This study was designed to identify a panel of tumor associated autoantibodies (TAAbs) in plasma to predict the clinical outcome of ICIs-based treatment in advanced NSCLC patients and correlation between TAAbs and checkpoint inhibitor pneumonitis (CIP) would also be investigated. Materials and Methods Baseline plasma was collected from patients with advanced NSCLC before receiving ICIs-based treatment. ELISA was used to detect concentration of autoantibodies. Clinical efficacy was evaluated according to RECIST v1.1. Results We have identified a panel of five-TAAbs to predict responses of ICIs-based treatment in a discovery cohort (n = 37), and confirmed its predictive value in a validation cohort (n = 129). In the validation cohort, the positivity of this 5-TAAbs panel was significantly associated with better response (ORR: 44.4% vs. 13.6%, P < 0.001) and longer PFS (7.6 vs. 3.3m, P < 0.001). This significant association was remained in subgroup of patients treated with combination therapy (ORR: 43.8% vs. 13.7%, P = 0.004,PFS: 6.7 vs. 3.7m, P = 0 .017). Furthermore, this 5-TAAs panel worked better in patients who received subsequent-line treatment (ORR: 42.4% vs. 7.7%, P = 0.001, PFS: 6.2 vs. 3.0m, P = 0.004) than those received first-line treatment (ORR: 46.7% vs. 35.7%, P = 0.345, PFS: NR vs. 10.48m, P = 0.146). In addition, the CIP incidence in patients with 5-TAAbs positive was significantly higher comparing to negative patients (20.4% vs. 5.9%, P = 0.015). Conclusion Our 5-TAAbs panel is a potential predictive biomarker for responses and toxicities to ICIs-based treatment in patients with advanced NSCLC.

Automated summary

The study identified a panel of five tumor associated autoantibodies (TAAbs) in plasma that can predict the clinical outcome of immunotherapy based treatment in patients with advanced non-small cell lung cancer. The positivity of this 5-TAAbs panel was significantly associated with better response and longer progression-free survival in a validation cohort. Additionally, the presence of these autoantibodies was correlated with a higher incidence of checkpoint inhibitor pneumonitis.