The CD40-CD154 Interaction Would Correlate with Proliferation and Immune Escape in Pancreatic Ductal Adenocarcinoma.

Background: CD40 and CD154 are associated with lymphocyte signaling pathways and they are also expressed in some malignant neoplasms, but the significance in pancreatic cancer is unknown.Methods: Eighty pancreatic cancer specimens were stained immunohistochemically, and the results were correlated with the patients' clinicopathologic features. Subsequently, in vitro analysis of CD40-CD154 signaling was performed.Result: Immunohistochemical analysis of tumor cells showed that 29 patients (36.3%) were positive for CD40, and 17 patients (21.3%) had very high CD154 expression. The survival of patients who had very high CD154 expression was significantly better than that of others (P = 0.0198). Univariate and multivariate analysis revealed that very high CD154 expression in cancer cells was not an independent, favorable prognostic factor (risk ratio, 0.493; P = 0.0224). On in vitro proliferation assay, the growth of PK-45P and KP-4 cells was blocked by CD40 and CD154 blocking antibodies. Moreover, on in vitro cytokine assay, Th-2 cytokines from PK-45P and SUIT-2 were blocked by CD40 or CD154 blocking antibody.Conclusion: These results suggest that the CD40-CD154 interaction would correlate with cell proliferation and secretion of cytokines in PDAC cells, and CD154 overexpression could be a favorable prognostic factor in PDAC patients. J. Surg. Oncol. 2011:103:230-238. (C) 2010 Wiley-Liss, Inc.