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Translational Research
Article . 2016 . Peer-reviewed
License: Elsevier TDM
Data sources: Crossref
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Protein disulfide isomerase A3–specific Th1 effector cells infiltrate colon cancer tissue of patients with circulating anti–protein disulfide isomerase A3 autoantibodies

Authors: CAORSI, Cristiana; Niccolai, Elena; CAPELLO, MICHELA; Vallone, Rosario; CHATTARAGADA, MICHELLE SAMUEL; ALUSHI, BRUNILDA; CASTIGLIONE, Anna; +8 Authors

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

Abstract

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.

Country
Italy
Keywords

Aged, 80 and over, Male, Immunity, Cellular, Autoantibodies; Colonic Neoplasms; Immunity; Lymphocytes, Tumor-Infiltrating; Male; Protein Disulfide-Isomerases; Th1 Cells;, Protein Disulfide-Isomerases, Dendritic Cells, Middle Aged, Th1 Cells, Immunity, Humoral, Lymphocytes, Tumor-Infiltrating, Colonic Neoplasms, Humans, Female, humoral immune response; colorectal-cancer; pancreatic cancer; hepatocellular carcinoma; differential expression; target antigens; ovarian cancer; ERP57; identification; vaccination, Medicine (all); Biochemistry (medical); Public Health, Environmental and Occupational Health, Aged, Autoantibodies

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
25
Top 10%
Average
Top 10%
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