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

Michela Capello, Jody V. Vykoukal, Hiroyuki Katayama, Leonidas E. Bantis, Hong Wang, Deepali L. Kundnani, Clemente Aguilar-Bonavides, Mitzi Aguilar, Satyendra C. Tripathi, 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 and Samir M. Hanash ()
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Michela Capello: The University of Texas MD Anderson Cancer Center
Jody V. Vykoukal: The University of Texas MD Anderson Cancer Center
Hiroyuki Katayama: The University of Texas MD Anderson Cancer Center
Leonidas E. Bantis: The University of Texas MD Anderson Cancer Center
Hong Wang: The University of Texas MD Anderson Cancer Center
Deepali L. Kundnani: The University of Texas MD Anderson Cancer Center
Clemente Aguilar-Bonavides: The University of Texas MD Anderson Cancer Center
Mitzi Aguilar: The University of Texas MD Anderson Cancer Center
Satyendra C. Tripathi: The University of Texas MD Anderson Cancer Center
Dilsher S. Dhillon: The University of Texas MD Anderson Cancer Center
Amin A. Momin: The University of Texas MD Anderson Cancer Center
Haley Peters: The University of Texas MD Anderson Cancer Center
Matthew H. Katz: The University of Texas MD Anderson Cancer Center
Hector Alvarez: The University of Texas MD Anderson Cancer Center
Vincent Bernard: The University of Texas MD Anderson Cancer Center
Sammy Ferri-Borgogno: The University of Texas MD Anderson Cancer Center
Randall Brand: University of Pittsburgh
Douglas G. Adler: University of Utah School of Medicine
Matthew A. Firpo: University of Utah School of Medicine
Sean J. Mulvihill: University of Utah School of Medicine
Jeffrey J. Molldrem: The University of Texas MD Anderson Cancer Center
Ziding Feng: The University of Texas MD Anderson Cancer Center
Ayumu Taguchi: The University of Texas MD Anderson Cancer Center
Anirban Maitra: The University of Texas MD Anderson Cancer Center
Samir M. Hanash: The University of Texas MD Anderson Cancer Center

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-018-08109-6

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