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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Capello M,Vykoukal JV,Katayama H,Bantis LE,Wang H,Kundnani DL,Aguilar-Bonavides C,Aguilar M,Tripathi SC,Dhillon DS,Momin AA,Peters H,Katz MH,Alvarez H,Bernard V,Ferri-Borgogno S,Brand R,Adler DG,Firpo MA,Mulvihill S

doi

10.1038/s41467-018-08109-6

subject

Has Abstract

pub_date

2019-01-16 00:00:00

pages

254

issue

1

issn

2041-1723

pii

10.1038/s41467-018-08109-6

journal_volume

10

pub_type

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