An integrated humoral and cellular response is elicited in pancreatic cancer by α‐enolase, a novel pancreatic ductal adenocarcinoma‐associated antigen

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a very poor 5‐year survival rate. α‐Enolase is a glycolytic enzyme that also acts as a surface plasminogen receptor. We find that it is overexpressed in PDAC and present on the cell surface of PDAC cell lines. The clinical correlation o...

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Bibliographic Details
Published in:International journal of cancer 2009-08, Vol.125 (3), p.639-648
Main Authors: Cappello, Paola, Tomaino, Barbara, Chiarle, Roberto, Ceruti, Patrizia, Novarino, Anna, Castagnoli, Carlotta, Migliorini, Paola, Perconti, Giovanni, Giallongo, Agata, Milella, Michele, Monsurrò, Vladia, Barbi, Stefano, Scarpa, Aldo, Nisticò, Paola, Giovarelli, Mirella, Novelli, Francesco
Format: Article
Language:English
Subjects:
alpha‐enolase
Animals
Antibodies, Neoplasm - immunology
Antibody Formation
Antigens, Neoplasm - immunology
B cell response
Biological and medical sciences
Blotting, Western
Carcinoma, Pancreatic Ductal - enzymology
Carcinoma, Pancreatic Ductal - immunology
Cell Line, Tumor
Cell Proliferation
Dendritic Cells - immunology
Gastroenterology. Liver. Pancreas. Abdomen
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
human
Humans
Immunity, Cellular
Immunoglobulin G - blood
Immunohistochemistry
Interferon-gamma - secretion
Keratinocytes - immunology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Mice
Pancreas - enzymology
Pancreas - immunology
pancreatic ductal adenocarcinoma
Pancreatic Neoplasms - enzymology
Pancreatic Neoplasms - immunology
Phosphopyruvate Hydratase - immunology
Phosphopyruvate Hydratase - metabolism
Skin - cytology
T cell response
T-Lymphocytes - immunology
T-Lymphocytes, Cytotoxic - immunology
tumor antigen
Tumors
Up-Regulation
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Description
Summary:Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a very poor 5‐year survival rate. α‐Enolase is a glycolytic enzyme that also acts as a surface plasminogen receptor. We find that it is overexpressed in PDAC and present on the cell surface of PDAC cell lines. The clinical correlation of its expression with tumor status has been reported for lung and hepatocellular carcinoma. We have previously demonstrated that sera from PDAC patients contain IgG autoantibodies to α‐enolase. The present work was intended to assess the ability of α‐enolase to induce antigen‐specific T cell responses. We show that α‐enolase‐pulsed dendritic cells (DC) specifically stimulate healthy autologous T cells to proliferate, secrete IFN‐γ and lyse PDAC cells but not normal cells. In vivo, α‐enolase‐specific T cells inhibited the growth of PDAC cells in immunodeficient mice. In 8 out of 12 PDAC patients with circulating IgG to α‐enolase, the existence of α‐enolase‐specific T cells was also demonstrated. Taken as a whole, these results indicate that α‐enolase elicits a PDAC‐specific, integrated humoral and cellular response. It is thus a promising and clinically relevant molecular target candidate for immunotherapeutic approaches as new adjuvants to conventional treatments in pancreatic cancer. © 2009 UICC
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.24355