title: An Autoimmune Response Signature Associated with the Development of Triple-Negative Breast Cancer Reflects Disease Pathogenesis.
abstract: The repertoire of antigens associated with the development of an autoimmune response in breast cancer has relevance to detection and treatment strategies. We have investigated the occurrence of autoantibodies associated with the development of triple-negative breast cancer (TNBC) in the before diagnosis setting and in samples collected at the time of diagnosis of TNBC. Lysate arrays containing protein fractions from the TNBC MDA-MB-231 cell line were hybridized with TNBC plasmas from the Women's Health Initiative cohort, collected before clinical diagnosis and with plasmas from matched controls. An immune response directed against spliceosome and glycolysis proteins was observed with case plasmas as previously reported in estrogen receptor(+) breast cancer. Importantly, autoantibodies directed against networks involving BRCA1, TP53, and cytokeratin proteins associated with a mesenchymal/basal phenotype were distinct to TNBC before diagnosis samples. Concordant autoantibody findings were observed with mouse plasma samples collected before occurrence of palpable tumors from a C3(1)-T triple negative mouse model. Plasma samples collected at the time of diagnosis of stage II TNBC and from matched healthy controls were subjected to proteomic analysis by mass spectrometry to identify Ig-bound proteins yielding a predominance of cytokeratins, including several associated with a mesenchymal/basal phenotype among cases compared with controls. Our data provide evidence indicative of a dynamic repertoire of antigens associated with a humoral immune response reflecting disease pathogenesis in TNBC.
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Katayama
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Clayton
authors.initials: C
authors.lastname: Boldt
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Jon J
authors.initials: JJ
authors.lastname: Ladd
authors.affiliation: Tumor Vaccine Group, University of Washington, Seattle, Washington.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Johnson
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Timothy
authors.initials: T
authors.lastname: Chao
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Michela
authors.initials: M
authors.lastname: Capello
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Suo
authors.affiliation: Tumor Vaccine Group, University of Washington, Seattle, Washington.
authors.forename: Jianning
authors.initials: J
authors.lastname: Mao
authors.affiliation: Division of Preventive Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Ross
authors.initials: R
authors.lastname: Prentice
authors.affiliation: Division of Hematology/Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, New York.
authors.forename: Francisco
authors.initials: F
authors.lastname: Esteva
authors.affiliation: MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Tumor Vaccine Group, University of Washington, Seattle, Washington.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Disis
authors.affiliation: MD Anderson Cancer Center, Houston, Texas. shanash@mdanderson.org.
authors.forename: Samir
authors.initials: S
authors.lastname: Hanash
mesh_terms: D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D019313:BRCA1 Protein / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006019:Glycolysis / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007633:Keratins / Q000276:immunology / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008875:Middle Aged; D020543:Proteome / Q000276:immunology / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D017381:Spliceosomes / Q000276:immunology*; D064726:Triple Negative Breast Neoplasms / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D019313:BRCA1 Protein; D007074:Immunoglobulin G; D020543:Proteome; D016159:Tumor Suppressor Protein p53; D007633:Keratins