title: The CD40-CD154 interaction would correlate with proliferation and immune escape in pancreatic ductal adenocarcinoma.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgical Oncology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. lindau99@infoseek.jp
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Shoji
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Keidai
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Roshan
authors.initials: R
authors.lastname: Mishra
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Ichinokawa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Tomoo
authors.initials: T
authors.lastname: Itoh
authors.forename: Toshiya
authors.initials: T
authors.lastname: Shinohara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondo
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology*; D015398:Signal Transduction; D019139:Tumor Escape
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand