Protein disulfide isomerase A3-specific Th1 effector cells infiltrate colon cancer tissue of patients with circulating anti-protein disulfide isomerase A3 autoantibodies

Transl Res. 2016 May:171:17-28.e1-2. doi: 10.1016/j.trsl.2015.12.013. Epub 2015 Dec 23.


To investigate novel colorectal cancer (CRC)-associated antigens that could be targets of humoral or cellular responses, we analyzed the reactivity of serum from a long-surviving CRC patient (for more than 100 months of follow-up) in clinical remission, by serologic proteome analysis. Two-dimensional Western blotting (2D-WB) and mass spectrometry analysis revealed a strong reactivity of this serum against protein disulfide isomerase A3 (PDIA3). Anti-PDIA3 antibodies are not a diagnostic marker of CRC, 2D-WB and Luminex analysis revealed that they were equally present in about 10% of sera from healthy subjects and CRC patients. Kaplan-Meier analysis of survival in CRC patient cohort, after 48 months of follow-up, showed a trend of higher survival in patients with increased levels of autoantibodies to PDIA3. Therefore, the interplay between the presence of these antibodies and T-cell response was investigated. Peripheral blood T cells from CRC patients with high immunoglobulin G (IgG) reactivity to PDIA3 also secreted interferon gamma (IFN-γ) when stimulated in vitro with recombinant PDIA3, whereas those from CRC with low IgG reactivity to PDIA3 did not. PDIA3-pulsed dendritic cells efficiently induced proliferation and IFN-γ production of autologous CD4(+) and CD8(+) T cells. Finally, ex vivo analysis of tumor-infiltrating T lymphocytes from CRC patients with autoantibodies to PDIA3 revealed that PDIA3-specific Th1 effector cells accumulated in tumor tissue. These data indicate that the presence of autoantibodies to PDIA3 favors the development of an efficient and specific T-cell response against PDIA3 in CRC patients. These results may be relevant for the design of novel immunotherapeutic strategies in CRC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Colonic Neoplasms / blood*
  • Colonic Neoplasms / immunology*
  • Dendritic Cells / immunology
  • Female
  • Humans
  • Immunity, Cellular / immunology
  • Immunity, Humoral / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Protein Disulfide-Isomerases / metabolism*
  • Th1 Cells / immunology*


  • Autoantibodies
  • Protein Disulfide-Isomerases
  • PDIA3 protein, human