Humoral immune responses toward tumor-derived antigens in previously untreated patients with chronic lymphocytic leukemia
| Autor: | Silvia Deaglio, Myriam Foglietta, Paola Cappello, Paolo Macor, Daniela Drandi, Candida Vitale, Valentina Griggio, Daniele Sblattero, Giorgia Mandili, Barbara Castella, Mario Boccadoro, Sara Serra, Michela Capello, Massimo Massaia, Roberto Chiarle, Silvia Peola, Paola Omedè, Marta Coscia, Francesco Novelli |
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| Přispěvatelé: | Griggio, Valentina, Mandili, Giorgia, Vitale, Candida, Capello, Michela, Macor, Paolo, Serra, Sara, Castella, Barbara, Peola, Silvia, Foglietta, Myriam, Drandi, Daniela, Omedé, Paola, Sblattero, Daniele, Cappello, Paola, Chiarle, Roberto, Deaglio, Silvia, Boccadoro, Mario, Novelli, Francesco, Massaia, Massimo, Coscia, Marta |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Proteomics Humoral responses Chronic lymphocytic leukemia Serological proteomics Apoptosis Immunogenetics Lymphocyte Activation Tumor antigens Serology hemic and lymphatic diseases Humoral responses chronic lymphocytic leukemia Humoral response Lymphocytes Hematology biology DNA-Binding Proteins Oncology Disease Progression Antibody Research Paper Alpha-enolase medicine.medical_specialty Serological proteomic 03 medical and health sciences Antigen Antigens Neoplasm Internal medicine medicine Biomarkers Tumor Humans Neoplasm Staging business.industry Tumor Suppressor Proteins Antibody-Dependent Cell Cytotoxicity Complement System Proteins medicine.disease Leukemia Lymphocytic Chronic B-Cell Immunity Humoral Transplantation 030104 developmental biology Phosphopyruvate Hydratase Immunology Antibody Formation biology.protein chronic lymphocytic leukemia Lymph Nodes business Tumor antigen Progressive disease Biomarkers |
| Zdroj: | Oncotarget |
| Popis: | // Valentina Griggio 1, 2 , Giorgia Mandili 2, 3 , Candida Vitale 1, 2 , Michela Capello 2, 3 , Paolo Macor 4 , Sara Serra 5 , Barbara Castella 1, 2, 3 , Silvia Peola 2, 3 , Myriam Foglietta 1, 2, 3 , Daniela Drandi 1, 2 , Paola Omede 1 , Daniele Sblattero 4 , Paola Cappello 2, 3, 6 , Roberto Chiarle 2, 3, 7 , Silvia Deaglio 5 , Mario Boccadoro 1, 2 , Francesco Novelli 2, 3, 6, 8 , Massimo Massaia 1, 2, 3 , Marta Coscia 1, 2 1 Division of Hematology, University of Torino, AOU Citta della Salute e della Scienza di Torino, Torino, Italy 2 Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy 3 Center for Experimental Research and Medical Studies (CeRMS), AOU Citta della Salute e della Scienza di Torino, Torino, Italy 4 Department of Life Sciences – University of Trieste, Trieste, Italy 5 Department of Medical Sciences, University of Torino and Immunogenetics Unit - Human Genetics Foundation (HuGeF), Torino, Italy 6 Molecular Biotechnology Center, Torino, Italy 7 Department of Pathology, Boston Children’s Hospital, Boston, Massachusetts, USA 8 Service of Immunogenetics and Transplantation, AOU Citta della Salute e della Scienza di Torino, Torino, Italy Correspondence to: Marta Coscia, email: marta.coscia@unito.it Keywords: chronic lymphocytic leukemia, humoral responses, tumor antigens, serological proteomics, alpha-enolase Received: July 13, 2016 Accepted: November 22, 2016 Published: November 30, 2016 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. |
| Databáze: | OpenAIRE |
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