Alpha-enolase elicits specific pancreatic adenocarcinoma specific-T cell responses in healthy donors and in tumor patients (48.4)

We have demonstrated that sera from pancreatic ductal adenocarcinoma (PDAC) patients contain IgG autoantibodies to α-enolase, a glycolytic enzyme that also works as surface plasminogen receptor. As this implies that α-enolase elicits a B-cell dependent humoral response in vivo in PDAC patients, its ability to induce a T cell mediated response to PDAC was investigated. Here we show that α-enolase-pulsed dendritic cells were capable to specifically stimulate healthy autologous T cells to proliferate, secrete IFN-γ and lyse PDAC cells. In vivo, α-enolase-specific T cells completely inhibited the growth of PDAC cells in immunodeficient mice. In PDAC patients, and in particular in those with circulating IgG autoantibodies to α-enolase, the existence of memory T cells to α-enolase was also demonstrated. As a whole, these results indicate that α-enolase elicits a PDAC-specific humoral and cellular responses. The sum of its features makes α-enolase a promising candidate for new immunotherapeutic strategies in the cure of PDAC that lacks until now of efficacious therapies to associate the conventional ones.