Research Papers:
Humoral immune responses toward tumor-derived antigens in previously untreated patients with chronic lymphocytic leukemia
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Abstract
Valentina Griggio1,2, Giorgia Mandili2,3, Candida Vitale1,2, Michela Capello2,3, Paolo Macor4, Sara Serra5, Barbara Castella1,2,3, Silvia Peola2,3, Myriam Foglietta1,2,3, Daniela Drandi1,2, Paola Omedé1, Daniele Sblattero4, Paola Cappello2,3,6, Roberto Chiarle2,3,7, Silvia Deaglio5, Mario Boccadoro1,2, Francesco Novelli2,3,6,8, Massimo Massaia1,2,3, Marta Coscia1,2
1Division of Hematology, University of Torino, AOU Città della Salute e della Scienza di Torino, Torino, Italy
2Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
3Center for Experimental Research and Medical Studies (CeRMS), AOU Città della Salute e della Scienza di Torino, Torino, Italy
4Department of Life Sciences – University of Trieste, Trieste, Italy
5Department of Medical Sciences, University of Torino and Immunogenetics Unit - Human Genetics Foundation (HuGeF), Torino, Italy
6Molecular Biotechnology Center, Torino, Italy
7Department of Pathology, Boston Children’s Hospital, Boston, Massachusetts, USA
8Service of Immunogenetics and Transplantation, AOU Città della Salute e della Scienza di Torino, Torino, Italy
Correspondence to:
Marta Coscia, email: [email protected]
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.
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