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

International Journal of Cancer - Tập 125 Số 3 - Trang 639-648 - 2009
Paola Cappello1, Barbara Tomaino, Roberto Chiarle, Paola Ceruti, Anna Novarino, Carlotta Castagnoli, Paola Migliorini, Giovanni Perconti, Agata Giallongo, Michèle Milella, Vladia Monsurrò, Stefano Barbi, Aldo Scarpa, Paola Nisticò, Mirella Giovarelli, Francesco Novelli
1Center for Experimental Research and Medical Studies, San Giovanni Battista Hospital, Torino, Italy.

Tóm tắt

AbstractPancreatic 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

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Tài liệu tham khảo

10.1038/nrc1630

10.1038/nrc2208

10.1038/nm1100

10.1146/annurev.immunol.22.012703.104803

10.1016/S0065-2776(06)90001-7

10.1158/0008-5472.CAN-07-0175

Berd D, 1986, Induction of cell‐mediated immunity to autologous melanoma cells and regression of metastases after treatment with a melanoma cell vaccine preceded by cyclophosphamide, Cancer Res, 46, 2572

10.1517/14712598.1.5.881

10.1084/jem.20042167

10.1158/1078-0432.CCR-07-0371

10.1007/s00262-004-0581-1

10.1084/jem.173.1.273

10.1002/1521-4141(200203)32:3<826::AID-IMMU826>3.0.CO;2-Y

10.1002/ijc.1205

10.1016/j.ejca.2007.08.028

10.1002/1615-9861(200110)1:10<1295::AID-PROT1295>3.0.CO;2-F

10.1016/S1357-4310(97)01081-2

NovelliF TomainoB CappelloP. Novel antigens and antibodies associated to pancreatic ductal adenocarcinoma. WO/2008/037792 2008. Available at:http://www.wipo.int/pctdb/en/wo.jsp?WO=2008037792.

10.1038/sj.gt.3300434

10.4161/cc.5.23.3525

10.4161/cc.6.3.3753

10.1093/biostatistics/4.2.249

10.1002/1521-4141(200012)30:12<3575::AID-IMMU3575>3.0.CO;2-#

10.1073/pnas.83.18.6741

10.4049/jimmunol.177.9.6143

10.1021/pr070281a

10.1097/01.sla.0000128681.76786.07

10.1002/ajh.10299

10.1093/jnci/95.7.516

10.1073/pnas.0502267102

10.1074/jbc.271.51.32529

10.1158/1078-0432.CCR-06-0324

10.1002/pmic.200401022

10.1007/s00417-006-0527-8

10.1111/j.1348-0421.2006.tb03776.x

10.1186/ar1845

10.1210/jc.87.2.752

10.1046/j.1365-2249.1998.00583.x

10.1016/S0896-8411(95)80027-1

10.1021/bi00220a034

10.1007/PL00000910

10.1073/pnas.0703342104

10.1073/pnas.0606512103

10.1056/NEJM199104113241504

10.1128/jb.174.21.6789-6799.1992

10.1093/infdis/169.2.452

10.1002/jcla.1860080405

10.1007/PL00014057

10.1038/nri2216

10.1111/j.1600-065X.2007.00576.x