An integrated humoral and cellular response is elicited in pancreatic cancer by alpha-enolase, a novel pancreatic ductal adenocarcinoma-associated antigen.
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with a very poor 5-year survival rate. alpha-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 alpha-enolase. The present work was intended to assess the ability of alpha-enolase to induce antigen-specific T cell responses. We show that alpha-enolase-pulsed dendritic cells (DC) specifically stimulate healthy autologous T cells to proliferate, secrete IFN-gamma and lyse PDAC cells but not normal cells. In vivo, alpha-enolase-specific T cells inhibited the growth of PDAC cells in immunodeficient mice. In 8 out of 12 PDAC patients with circulating IgG to alpha-enolase, the existence of alpha-enolase-specific T cells was also demonstrated. Taken as a whole, these results indicate that alpha-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.
Cappello
Paola
P
Center for Experimental Research and Medical Studies, San Giovanni Battista Hospital, Torino, Italy.
Tomaino
Barbara
B
Chiarle
Roberto
R
Ceruti
Patrizia
P
Novarino
Anna
A
Castagnoli
Carlotta
C
Migliorini
Paola
P
Perconti
Giovanni
G
Giallongo
Agata
A
Milella
Michele
M
Monsurrò
Vladia
V
Barbi
Stefano
S
Scarpa
Aldo
A
Nisticò
Paola
P
Giovarelli
Mirella
M
Novelli
Francesco
F
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000276:immunology*; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology; D051379:Mice; D010179:Pancreas / Q000201:enzymology / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000276:immunology*; D010751:Phosphopyruvate Hydratase / Q000276:immunology / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015854:Up-Regulation
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G; D007371:Interferon-gamma; D010751:Phosphopyruvate Hydratase