PURPOSE: We investigated whether inhibition of interleukin 6 (IL-6) has 
therapeutic activity in ovarian cancer via abrogation of a tumor-promoting 
cytokine network.
EXPERIMENTAL DESIGN: We combined preclinical and in silico experiments with a 
phase 2 clinical trial of the anti-IL-6 antibody siltuximab in patients with 
platinum-resistant ovarian cancer.
RESULTS: Automated immunohistochemistry on tissue microarrays from 221 ovarian 
cancer cases showed that intensity of IL-6 staining in malignant cells 
significantly associated with poor prognosis. Treatment of ovarian cancer cells 
with siltuximab reduced constitutive cytokine and chemokine production and also 
inhibited IL-6 signaling, tumor growth, the tumor-associated macrophage 
infiltrate and angiogenesis in IL-6-producing intraperitoneal ovarian cancer 
xenografts. In the clinical trial, the primary endpoint was response rate as 
assessed by combined RECIST and CA125 criteria. One patient of eighteen 
evaluable had a partial response, while seven others had periods of disease 
stabilization. In patients treated for 6 months, there was a significant decline 
in plasma levels of IL-6-regulated CCL2, CXCL12, and VEGF. Gene expression 
levels of factors that were reduced by siltuximab treatment in the patients 
significantly correlated with high IL-6 pathway gene expression and macrophage 
markers in microarray analyses of ovarian cancer biopsies.
CONCLUSION: IL-6 stimulates inflammatory cytokine production, tumor 
angiogenesis, and the tumor macrophage infiltrate in ovarian cancer and these 
actions can be inhibited by a neutralizing anti-IL-6 antibody in preclinical and 
clinical studies.