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