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

• DOI: 10.1038/s41467-018-08109-6
• Publication Date: 2019-01-10T13:10:46Z
• Authors: Michela Capello; Jody V. Vykoukal; Hiroyuki Katayama; Leonidas E. Bantis; Hong Wang; Deepali L. Kundnani; Clemente Aguilar-...; Mitzi Aguilar; Satyendra C. Trip...; 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
• Keywords: Exosome

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