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.
Center for Experimental Research and Medical Studies, San Giovanni Battista Hospital, Torino, Italy.
Paola
P
Cappello
Barbara
B
Tomaino
Roberto
R
Chiarle
Patrizia
P
Ceruti
Anna
A
Novarino
Carlotta
C
Castagnoli
Paola
P
Migliorini
Giovanni
G
Perconti
Agata
A
Giallongo
Michele
M
Milella
Vladia
V
Monsurrò
Stefano
S
Barbi
Aldo
A
Scarpa
Paola
P
Nisticò
Mirella
M
Giovarelli
Francesco
F
Novelli
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