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


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.

  • Adler DG
  • Aguilar M
  • Aguilar-Bonavides C
  • Alvarez H
  • Bantis LE
  • Bernard V
  • Brand R
  • Capello M
  • Dhillon DS
  • Feng Z
  • Ferri-Borgogno S
  • Firpo MA
  • Hanash SM
  • Katayama H
  • Katz MH
  • Kundnani DL
  • Maitra A
  • Molldrem JJ
  • Momin AA
  • Mulvihill SJ
  • Peters H
  • Taguchi A
  • Tripathi SC
  • Vykoukal JV
  • Wang H
PubMed ID
Appears In
Nat Commun, 2019, 10 (1)