title: Humoral immune responses toward tumor-derived antigens in previously untreated patients with chronic lymphocytic leukemia.
abstract: In chronic lymphocytic leukemia (CLL) the occurrence and the impact of antibody responses toward tumor-derived antigens are largely unexplored. Our serological proteomic data show that antibodies toward 47 identified antigens are detectable in 29 out of 35 patients (83%) with untreated CLL. The glycolytic enzyme alpha-enolase (ENO1) is the most frequently recognized antigen (i.e. 54% of CLL sera). We show that ENO1 is upregulated in the proliferating B-cell fraction of CLL lymph nodes. In CLL cells of the peripheral blood, ENO1 is exclusively expressed at the intracellular level, whereas it is exposed on the surface of apoptotic leukemic cells.From the clinical standpoint, patients with progressive CLL show a higher number of antigen recognitions compared to patients with stable disease. Consistently, the anti-ENO1 antibodies are prevalent in sera from patients with progressive disease and their presence is predictive of a shorter time to first treatment. This clinical inefficacy associates with the inability of patients' sera to trigger complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity against leukemic cells.Together, these results indicate that antibody responses toward tumor-derived antigens are frequently detectable in sera from patients with CLL, but they are expression of a disrupted immune system and unable to hamper disease progression.
authors.affiliation: Division of Hematology, University of Torino, AOU Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Griggio
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Mandili
authors.affiliation: Division of Hematology, University of Torino, AOU Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Candida
authors.initials: C
authors.lastname: Vitale
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Capello
authors.affiliation: Department of Life Sciences - University of Trieste, Trieste, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Macor
authors.affiliation: Department of Medical Sciences, University of Torino and Immunogenetics Unit - Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Serra
authors.affiliation: Division of Hematology, University of Torino, AOU Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Castella
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Peola
authors.affiliation: Division of Hematology, University of Torino, AOU Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Myriam
authors.initials: M
authors.lastname: Foglietta
authors.affiliation: Division of Hematology, University of Torino, AOU Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Drandi
authors.affiliation: Division of Hematology, University of Torino, AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Omedé
authors.affiliation: Department of Life Sciences - University of Trieste, Trieste, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Sblattero
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, Torino, Italy.|Molecular Biotechnology Center, Torino, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cappello
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Chiarle
authors.affiliation: Department of Medical Sciences, University of Torino and Immunogenetics Unit - Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
authors.affiliation: Division of Hematology, University of Torino, AOU Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Boccadoro
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, Torino, Italy.|Molecular Biotechnology Center, Torino, Italy.|Service of Immunogenetics and Transplantation, AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Novelli
authors.affiliation: Division of Hematology, University of Torino, AOU Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.|Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, Torino, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Massaia
authors.affiliation: Division of Hematology, University of Torino, AOU Città della Salute e della Scienza di Torino, Torino, Italy.|Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Coscia
mesh_terms: D000917:Antibody Formation / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D056724:Immunity, Humoral; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D009367:Neoplasm Staging; D010751:Phosphopyruvate Hydratase / Q000276:immunology / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D025521:Tumor Suppressor Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D003165:Complement System Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase
keywords: alpha-enolase; chronic lymphocytic leukemia; humoral responses; serological proteomics; tumor antigens