Tumor-derived Autoantibodies Identify Malignant Pulmonary Nodules

Area of Science:

• Immunology
• Oncology
• Biomarker Discovery

Background:

• Lung cancer screening reduces mortality but increases harm from invasive follow-up of benign nodules.
• Tumorigenesis triggers immune responses, offering potential for tumor-specific biomarkers.
• Need for noninvasive methods to differentiate malignant from benign pulmonary nodules.

Purpose of the Study:

• To identify and profile tumor-derived autoantibodies as peripheral biomarkers for malignant pulmonary nodules.
• To assess the diagnostic potential of these autoantibodies in patient plasma.

Main Methods:

• High-density protein arrays used to define autoantibody specificities from lung tumor B cells.
• Analysis of autoantibodies (free or antigen-complexed) in plasma from lung cancer patients and benign nodule controls.
• Validation of promising autoantibodies in an independent cohort of 250 nodule-positive patients.

Main Results:

• Thirteen autoantibodies isolated ex vivo demonstrated ≥50% sensitivity and ≥70% specificity for lung cancer.
• Eleven of 13 autoantibodies were detected in plasma, either free or complexed with antigen.
• Five autoantibodies remained significantly elevated in cancers in the validation cohort; four detected malignant nodules with AUCs of 0.74-0.78.

Conclusions:

• A novel pipeline successfully identified tumor-derived autoantibodies as potential blood biomarkers for malignant pulmonary nodules.
• This autoantibody-based approach offers a cost-effective and noninvasive method for nodule malignancy determination.
• Future implications for widespread low-dose computed tomography screening to improve lung cancer diagnosis.