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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.
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
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
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). | 25 | |
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. | Top 10% | |
influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Average | |
impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 10% |