AUTHOR=Zhou Juan , Zhao Jing , Jia Qingzhu , Chu Qian , Zhou Fei , Chu Xiangling , Zhao Wencheng , Ren Shengxiang , Zhou Caicun , Su Chunxia 

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

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.625578

DOI=10.3389/fonc.2021.625578

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Materials and Methods</title><p>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.</p></sec><sec><title>Results</title><p>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%, <italic>P</italic> &lt; 0.001) and longer PFS (7.6 vs. 3.3m, <italic>P</italic> &lt; 0.001). This significant association was remained in subgroup of patients treated with combination therapy (ORR: 43.8% vs. 13.7%, <italic>P</italic> = 0.004,PFS: 6.7 vs. 3.7m, <italic>P</italic> = 0 .017). Furthermore, this 5-TAAs panel worked better in patients who received subsequent-line treatment (ORR: 42.4% vs. 7.7%, <italic>P</italic> = 0.001, PFS: 6.2 vs. 3.0m, <italic>P</italic> = 0.004) than those received first-line treatment (ORR: 46.7% vs. 35.7%, <italic>P</italic> = 0.345, PFS: NR vs. 10.48m, <italic>P</italic> = 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%, <italic>P</italic> = 0.015).</p></sec><sec><title>Conclusion</title><p>Our 5-TAAbs panel is a potential predictive biomarker for responses and toxicities to ICIs-based treatment in patients with advanced NSCLC.</p></sec>