Exosomes harbor B cell targets in pancreatic adenocarcinoma and exert decoy function against complement-mediated cytotoxicity.

Abstract

Although B cell response is frequently found in cancer, there is little evidence that it alters tumor development or progression. The process through which tumor-associated antigens trigger humoral response is not well delineated. We investigate the repertoire of antigens associated with humoral immune response in pancreatic ductal adenocarcinoma (PDAC) using in-depth proteomic profiling of immunoglobulin-bound proteins from PDAC patient plasmas and identify tumor antigens that induce antibody response together with exosome hallmark proteins. Additional profiling of PDAC cell-derived exosomes reveals significant overlap in their protein content with immunoglobulin-bound proteins in PDAC plasmas, and significant autoantibody reactivity is observed between PDAC cell-derived exosomes and patient plasmas compared to healthy controls. Importantly, PDAC-derived exosomes induce a dose-dependent inhibition of PDAC serum-mediated complement-dependent cytotoxicity towards cancer cells. In summary, we provide evidence that exosomes display a large repertoire of tumor antigens that induce autoantibodies and exert a decoy function against complement-mediated cytotoxicity.

• Authors: Michela Capello, Jody V Vykoukal, Hiroyuki Katayama, Leonidas E Bantis, Hong Wang, Deepali L Kundnani, Clemente Aguilar-Bonavides, Mitzi Aguilar, Satyendra C Tripathi, Dilsher S Dhillon, Amin A Momin, Haley Peters, Matthew H Katz, Hector Alvarez, Vincent Bernard, Sammy Ferri-Borgogno, Randall Brand, Douglas G Adler, Matthew A Firpo, Sean J Mulvihill, Jeffrey J Molldrem, Ziding Feng, Ayumu Taguchi, Anirban Maitra, Samir M Hanash
• Journal: Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 254 (01 16 2019) ISSN: 2041-1723 [Electronic] England
• PMID: 30651550 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Autoantibodies
• Complement System Proteins

Topics

• Aged
• Aged, 80 and over
• Antibody Formation (immunology)
• Antigens, Neoplasm (immunology, metabolism)
• Autoantibodies (immunology)
• B-Lymphocytes (immunology)
• Carcinoma, Pancreatic Ductal (blood, immunology)
• Cell Line, Tumor
• Cohort Studies
• Complement System Proteins (immunology)
• Datasets as Topic
• Exosomes (immunology, metabolism, ultrastructure)
• Female
• Gene Expression Profiling
• Healthy Volunteers
• Humans
• Male
• Microscopy, Electron
• Middle Aged
• Pancreatic Neoplasms (blood, immunology)
• Proteomics (methods)
• Sequence Analysis, RNA