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; Samir M. Hanash

doi:10.1038/s41467-018-08109-6

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. MulvihillJeffrey J. Molldrem, Ziding Feng, Ayumu Taguchi, Anirban Maitra, Samir M. Hanash

Research output: Contribution to journal › Article › peer-review

118 Scopus citations

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.

Original language	English (US)
Article number	254
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-08109-6
State	Published - Dec 1 2019

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Capello, M., Vykoukal, J. V., Katayama, H., Bantis, L. E., Wang, H., Kundnani, D. L., Aguilar-Bonavides, C., Aguilar, M., Tripathi, S. C., Dhillon, D. S., Momin, A. A., Peters, H., Katz, M. H., Alvarez, H., Bernard, V., Ferri-Borgogno, S., Brand, R., Adler, D. G., Firpo, M. A., ... Hanash, S. M. (2019). Exosomes harbor B cell targets in pancreatic adenocarcinoma and exert decoy function against complement-mediated cytotoxicity. Nature communications, 10(1), Article 254. https://doi.org/10.1038/s41467-018-08109-6

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, SJ, Molldrem, JJ, Feng, Z, Taguchi, A, Maitra, A & Hanash, SM 2019, 'Exosomes harbor B cell targets in pancreatic adenocarcinoma and exert decoy function against complement-mediated cytotoxicity', Nature communications, vol. 10, no. 1, 254. https://doi.org/10.1038/s41467-018-08109-6

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title = "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.",

author = "Michela Capello and Vykoukal, {Jody V.} and Hiroyuki Katayama and Bantis, {Leonidas E.} and Hong Wang and Kundnani, {Deepali L.} and Clemente Aguilar-Bonavides and Mitzi Aguilar and Tripathi, {Satyendra C.} and Dhillon, {Dilsher S.} and Momin, {Amin A.} and Haley Peters and Katz, {Matthew H.} and Hector Alvarez and Vincent Bernard and Sammy Ferri-Borgogno and Randall Brand and Adler, {Douglas G.} and Firpo, {Matthew A.} and Mulvihill, {Sean J.} and Molldrem, {Jeffrey J.} and Ziding Feng and Ayumu Taguchi and Anirban Maitra and Hanash, {Samir M.}",

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AU - Capello, Michela

AU - Vykoukal, Jody V.

AU - Katayama, Hiroyuki

AU - Bantis, Leonidas E.

AU - Wang, Hong

AU - Kundnani, Deepali L.

AU - Aguilar-Bonavides, Clemente

AU - Aguilar, Mitzi

AU - Tripathi, Satyendra C.

AU - Dhillon, Dilsher S.

AU - Momin, Amin A.

AU - Peters, Haley

AU - Katz, Matthew H.

AU - Alvarez, Hector

AU - Bernard, Vincent

AU - Ferri-Borgogno, Sammy

AU - Brand, Randall

AU - Adler, Douglas G.

AU - Firpo, Matthew A.

AU - Mulvihill, Sean J.

AU - Molldrem, Jeffrey J.

AU - Feng, Ziding

AU - Taguchi, Ayumu

AU - Maitra, Anirban

AU - Hanash, Samir M.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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