The soluble HLA peptidome of pleural effusions is a valuable source for tumor antigens

Pleural effusions are excess fluids that accumulate within the pleural cavity of lungs, due to both malignant and benign diseases. The fluids contain cells and soluble molecules that could be used for diagnostic purposes. Our research goal is to analyze the soluble human leukocyte antigen (HLA) peptidome from pleural effusions in order to develop a better lung cancer diagnosis and to identify tumor antigens candidates for immunotherapy. HLA molecules are normally expressed on the surface of all nucleated cells but are also secreted to the plasma, and other body fluids, with their original cargo peptides. The Admon lab has previously analyzed the soluble HLA peptidome of human plasma and here we extend this idea to pleural effusions. For this purpose, we used ~500 ml of pleural effusion samples collected from 14 patients, 5 suffering from heart and/or renal failure and 9 cancer patients. The membranal and soluble HLA peptidomes of each individual patient correlated to each other. Additionally, soluble pleural effusions HLA peptidomes from the same patient, obtained at different visits to the clinic, were highly similar. Compared with benign effusions, the soluble HLA peptidomes of malignant pleural effusions were larger and included HLA peptides derived from known tumor-associated antigens, including cancer/testis antigens, lung-related proteins, and VEGF pathway proteins. Importantly, selected tumor-associated antigens that were identified by the immunopeptidomics were able to successfully prime CD8+ T cells. We therefore suggest that pleural effusion HLA peptidome of patients with malignant tumors can serve as a source of biomarkers for tumor diagnosis and personalized immunotherapy.