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


Nat Commun, 2019, 10 (1)

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