Expression of CD40 and growth-inhibitory activity of CD40 ligand in ovarian cancer cell lines

Gynecol Oncol. 2007 Mar;104(3):707-13. doi: 10.1016/j.ygyno.2006.10.056. Epub 2006 Dec 12.


Objective: Soluble recombinant human CD40 ligand trimer (rhuCD40Lt) has shown antitumor activity in preclinical and clinical studies. We evaluated the effect of rhuCD40Lt on epithelial ovarian carcinoma (EOC) cell lines.

Methods: Expression of the receptor, CD40, was determined by reverse transcriptase-polymerase chain reaction and flow cytometry, and antiproliferative effects of rhuCD40Lt, either alone or in combination with recombinant interferon-gamma (rIFN-gamma), were examined in 8 EOC lines.

Results: Expression of CD40 was elevated in 5 out of 8 EOC cell lines examined by flow cytometry, and the presence of CD40 transcripts was detected by RT-PCR in all 8 cell lines. CD40 expression was increased by rIFN-gamma, but treatment with rhuCD40Lt decreased CD40 expression in 4 of the 5 lines that had shown elevated CD40 expression. rhuCD40Lt had a growth-inhibitory effect on 2774 cells, which also exhibited the highest level of CD40 expression. Growth-inhibitory effect of rhuCD40Lt was additive with rIFN-gamma on 2774, NMP-1, a cisplatin-resistant subline of OVCAR3, and HEY cell lines. The number of apoptotic tumor cells was increased following treatment with rhuCD40Lt.

Conclusions: CD40 is expressed on EOC cell lines, and expression was found at the transcript level in all of the EOC lines examined. rIFN-gamma enhances CD40 expression, though a decrease in CD40 expression was observed following treatment with rhuCD40Lt. Growth-inhibitory activity of rhuCD40Lt on EOC lines that express CD40 could be enhanced when rhuCD40Lt treatment was combined with rIFN-gamma. These results suggest that future studies of the combination of rhuCD40Lt and rIFN-gamma might warrant consideration.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • CD40 Antigens / biosynthesis*
  • CD40 Ligand / administration & dosage
  • CD40 Ligand / pharmacology*
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Female
  • Flow Cytometry
  • Humans
  • Interferon-gamma / administration & dosage
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction


  • CD40 Antigens
  • Recombinant Proteins
  • CD40 Ligand
  • Interferon-gamma