Modulation of CD3-zeta as a marker of clinical response to IL-2 therapy in ovarian cancer patients

Gynecol Oncol. 2004 Jul;94(1):54-60. doi: 10.1016/j.ygyno.2004.03.032.


Objective: In women with advanced ovarian cancer, levels of CD3-zeta on peripheral blood lymphocytes have previously been demonstrated to correlate with responsiveness to interleukin (IL)-2 therapy. The aims of this study were to identify the circulating component that modulated zeta expression and to define whether this suppressive activity could serve as a marker of biotherapy responsiveness.

Methods: Sera were obtained from 17 patients with advanced ovarian cancer treated with intraperitoneal IL-2 in a phase I trial between 1987 and 1990. Nine of these patients exhibited a clinical response, while eight did not respond. Six additional sera from age-matched, noncancer-bearing women were used as controls. Jurkat E6-1 cells were used to assay modulation of CD3-zeta by sera and serum-derived components. Jurkat cells were exposed to serum or chromatographically fractionated serum components for 4 days and zeta expression was analyzed by Western immunoblots and quantitated by densitometry.

Results: The effect of sera on zeta expression was compared between responders and nonresponders. Incubation of Jurkat cells with sera from responders suppressed CD3-zeta expression by 36.7% (vs. control treated), while treatment with sera from nonresponders produced an 83.7% reduction in zeta expression (difference between groups, P < 0.001). When sera from nonresponders were chromatographically fractionated, a <20 kDa component was identified that correlated with decreased zeta chain expression. This component was diminished in the sera of responders and absence in controls.

Conclusions: Thus, in patients with advanced ovarian cancer, a circulating component, which decreases zeta expression, can be identified as a marker for responsiveness to IL-2 therapy.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / blood*
  • CD3 Complex / biosynthesis
  • CD3 Complex / blood*
  • Environmental Monitoring / methods
  • Female
  • Humans
  • Interleukin-2 / therapeutic use*
  • Jurkat Cells
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / drug therapy*


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CD3 Complex
  • CD3 antigen, zeta chain
  • Interleukin-2