6533b861fe1ef96bd12c5930
RESEARCH PRODUCT
An integrated humoral and cellular response is elicited in pancreatic cancer by alpha-enolase, a novel pancreatic ductal adenocarcinoma-associated antigen
Carlotta CastagnoliBarbara TomainoGiovanni PercontiPaola MiglioriniAnna NovarinoPatrizia CerutiVladia MonsurròMirella GiovarelliMichele MilellaPaola CappelloAldo ScarpaAgata GiallongoRoberto ChiarleFrancesco NovelliPaola NisticòStefano Barbisubject
KeratinocytesCancer ResearchPancreatic diseaseendocrine system diseasesalpha-enolaseAntibodies NeoplasmAlpha-enolaseT-LymphocytesMiceSkinImmunity Cellularhuman; pancreatic ductal adenocarcinoma; alpha enolase; tumor antigen; B cell response; T cell responsebiologyalpha enolasehuman; pancreatic ductal adenocarcinoma; alpha-enolase; tumor antigen; B cell response; T cell responseImmunohistochemistryTumor antigenUp-RegulationGene Expression Regulation Neoplasticmedicine.anatomical_structureOncologyAntibodyCarcinoma Pancreatic DuctalB cell responseT cellBlotting Westernpancreatic ductal adenocarcinomaGene Expression Regulation EnzymologicInterferon-gammaImmune systemAntigenAntigens NeoplasmCell Line TumorPancreatic cancermedicineAnimalsHumanshumanPancreasCell ProliferationDendritic Cellsmedicine.diseaseT cell responsepancreatic ductal adenocarcinoma; alpha-enolase; tumor antigen.digestive system diseasesPancreatic NeoplasmsImmunoglobulin GPhosphopyruvate HydrataseAntibody FormationImmunologybiology.proteintumor antigenT-Lymphocytes Cytotoxicdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2009-08-01 |