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The CD40‐CD154 interaction would correlate with proliferation and immune escape in pancreatic ductal adenocarcinoma
Author(s) -
Shoji Yasuhito,
Miyamoto Masaki,
Ishikawa Keidai,
Yoshioka Tatsuya,
Mishra Roshan,
Ichinokawa Kazuomi,
Matsumura Yoshiyuki,
Itoh Tomoo,
Shinohara Toshiya,
Hirano Satoshi,
Kondo Satoshi
Publication year - 2010
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.21812
Subject(s) - cd154 , cd40 , pancreatic cancer , cancer research , medicine , immune system , cancer , immunohistochemistry , cytokine , pathology , in vitro , biology , immunology , cytotoxic t cell , biochemistry
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. © 2010 Wiley‐Liss, Inc.