Abstract
Pancreatic Ductal Adenocarcinoma (PDA) is an aggressive malignancy with a very poor outcome. Although chemotherapy (CT) treatment has poor efficacy, it can enhance tumor immunogenicity. Tumor-Associated Antigens (TAA) are self-proteins that are overexpressed in tumors that may induce antibody production and can be PDA theranostic targets. However, the prognostic value of TAA-antibody association as Circulating Immune Complexes (CIC) has not yet been elucidated, mainly due to the lack of techniques that lead to their identification. In this study, we show a novel method to separate IgG, IgM, and IgA CIC from sera to use them as prognostic biomarkers of CT response. The PDA Immune-Complexome (IC) was identified using a LTQ-Orbitrap mass spectrometer followed by computational analysis. The analysis of the IC of 37 PDA patients before and after CT revealed differential associated antigens (DAA) for each immunoglobulin class. Our method identified different PDA-specific CIC in patients that were associated with poor prognosis patients. Finally, CIC levels were significantly modified by CT suggesting that they can be used as effective prognostic biomarkers to follow CT response in PDA patients.
Highlights
The role of the immune system in cancer has been extensively studied, due to its critical role in counteracting tumor development
We have demonstrated that, in Pancreatic Ductal Adenocarcinoma (PDA), identifying novel Tumor-Associated Antigens (TAA) associated with different classes of Ig patients treated with CT can provide new prognostic markers
We performed a systematic analysis of the PDA IC
Summary
The role of the immune system in cancer has been extensively studied, due to its critical role in counteracting tumor development. (i.e., with a low infiltrate of T cells), such as pancreatic cancer, the possibility to exploit the immune system to identify biomarkers or immunological targets has been demonstrated [2,3,4,5,6,7]. IC are removed from the bloodstream, while, in pathological conditions, CIC can accumulate in the bloodstream or in different tissues, especially in the kidneys, inducing glomerulonephritis [8]. The accumulation of CIC could provide a novel source of biomarkers for the diagnosis and the follow-up of a pathological condition. The use of CIC as disease biomarkers was studied for autoimmune diseases, such as systemic lupus erythematosus [9,10] and rheumatoid arthritis [8], but it was observed in other pathologies, including infectious diseases and acquired thrombotic thrombocytopenic purpura [8,11,12]. A systematic analysis of CIC was provided only in 2013 in uveitis, using pull-down assays to separate
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