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

作者:Shoji Yasuhito*; Miyamoto Masaki; Ishikawa Keidai; Yoshioka Tatsuya; Mishra Roshan; Ichinokawa Kazuomi; Matsumura Yoshiyuki; Itoh Tomoo; Shinohara Toshiya; Hirano Satoshi; Kondo Satoshi
来源:Journal of Surgical Oncology, 2011, 103(3): 230-238.
DOI:10.1002/jso.21812

摘要

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.

  • 出版日期2011-3-1