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Am J Respir Crit Care Med. 2019 May 15;199(10):1257-1266. doi: 10.1164/rccm.201804-0628OC.

Tumor-derived Autoantibodies Identify Malignant Pulmonary Nodules.

Author information

1 Translational Research Program, Public Health Sciences.
2 Human Biology Division.
3 Clinical Research Division.
4 Otto Loewi Research Center, Pharmacology Section, Medical University of Graz, Graz, Austria.
5 Program in Biostatistics and Biomathematics, Division of Public Health Sciences, and.
6 Department of Radiology, University of Washington, Seattle, Washington; and.
7 Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
8 Division of Pulmonary and Critical Care, Fred Hutchinson Cancer Research Center, Seattle, Washington.


Rationale: Screening for non-small cell lung cancer is associated with earlier diagnosis and reduced mortality but also increased harm caused by invasive follow-up of benign pulmonary nodules. Lung tumorigenesis activates the immune system, components of which could serve as tumor-specific biomarkers. Objectives: To profile tumor-derived autoantibodies as peripheral biomarkers of malignant pulmonary nodules. Methods: High-density protein arrays were used to define the specificity of autoantibodies isolated from B cells of 10 resected lung tumors. These tumor-derived autoantibodies were also examined as free or complexed to antigen in the plasma of the same 10 patients and matched benign nodule control subjects. Promising autoantibodies were further analyzed in an independent cohort of 250 nodule-positive patients. Measurements and Main Results: Thirteen tumor B-cell-derived autoantibodies isolated ex vivo showed greater than or equal to 50% sensitivity and greater than or equal to 70% specificity for lung cancer. In plasma, 11 of 13 autoantibodies were present both complexed to and free from antigen. In the larger validation cohort, 5 of 13 tumor-derived autoantibodies remained significantly elevated in cancers. A combination of four of these autoantibodies could detect malignant nodules with an area under the curve of 0.74 and had an area under the curve of 0.78 in a subcohort of indeterminate (8-20 mm in the longest diameter) pulmonary nodules. Conclusions: Our novel pipeline identifies tumor-derived autoantibodies that could effectively serve as blood biomarkers for malignant pulmonary nodule diagnosis. This approach has future implications for both a cost-effective and noninvasive approach to determine nodule malignancy for widespread low-dose computed tomography screening.


B cells; computed tomography imaging; early detection; indeterminate pulmonary nodules; lung cancer


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