Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 17 - 28 |
| Number of pages | 12 |
| Journal | Translational Research |
| Volume | 171 |
| DOIs | |
| Publication status | Published - May 1 2016 |
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ASJC Scopus subject areas
- Medicine(all)
- Public Health, Environmental and Occupational Health
- Biochemistry, medical
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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. / Caorsi, Cristiana; Niccolai, Elena; Capello, Michela; Vallone, Rosario; Chattaragada, Michelle S.; Alushi, Brunilda; Castiglione, Anna; Ciccone, Gianni; Mautino, Alessandro; Cassoni, Paola; De Monte, Lucia; Álvarez-Fernández, Sheila M.; Amedei, Amedeo; Alessio, Massimo; Novelli, Francesco.
In: Translational Research, Vol. 171, 01.05.2016, p. 17 - 28.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Protein disulfide isomerase A3-specific Th1 effector cells infiltrate colon cancer tissue of patients with circulating anti-protein disulfide isomerase A3 autoantibodies
AU - Caorsi, Cristiana
AU - Niccolai, Elena
AU - Capello, Michela
AU - Vallone, Rosario
AU - Chattaragada, Michelle S.
AU - Alushi, Brunilda
AU - Castiglione, Anna
AU - Ciccone, Gianni
AU - Mautino, Alessandro
AU - Cassoni, Paola
AU - De Monte, Lucia
AU - Álvarez-Fernández, Sheila M.
AU - Amedei, Amedeo
AU - Alessio, Massimo
AU - Novelli, Francesco
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.trsl.2015.12.013
DO - 10.1016/j.trsl.2015.12.013
M3 - Article
VL - 171
SP - 17
EP - 28
JO - Translational Research
JF - Translational Research
SN - 1931-5244
ER -