Humoral immune responses toward tumor-derived antigens in previously untreated patients with chronic lymphocytic leukemia

Oncotarget. 2017 Jan 10;8(2):3274-3288. doi: 10.18632/oncotarget.13712.

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.

Keywords: alpha-enolase; chronic lymphocytic leukemia; humoral responses; serological proteomics; tumor antigens.

MeSH terms

  • Antibody Formation / immunology
  • Antibody-Dependent Cell Cytotoxicity
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism
  • Apoptosis / genetics
  • Apoptosis / immunology
  • Biomarkers
  • Biomarkers, Tumor / immunology
  • Biomarkers, Tumor / metabolism
  • Complement System Proteins / immunology
  • Complement System Proteins / metabolism
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Humans
  • Immunity, Humoral*
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymphocyte Activation / immunology
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Neoplasm Staging
  • Phosphopyruvate Hydratase / immunology
  • Phosphopyruvate Hydratase / metabolism
  • Proteomics / methods
  • Tumor Suppressor Proteins / immunology
  • Tumor Suppressor Proteins / metabolism

Substances

  • Antigens, Neoplasm
  • Biomarkers
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • Complement System Proteins
  • ENO1 protein, human
  • Phosphopyruvate Hydratase