Serum vascular endothelial growth factor and fibronectin predict clinical response to high-dose interleukin-2 therapy

J Clin Oncol. 2009 Jun 1;27(16):2645-52. doi: 10.1200/JCO.2008.19.1106. Epub 2009 Apr 13.


Purpose: High-dose interleukin-2 (IL-2) induces durable therapeutic responses in a small subset of patients with metastatic melanoma and renal cell carcinoma, but simple pretreatment predictors of response have not been identified.

Patients and methods: To identify predictive biomarkers of clinical response, sera from patients treated with high-dose IL-2 were collected for analysis using a customized, multiplex antibody-targeted protein array platform that surveyed expression of soluble factors associated with tumor immunobiology. Soluble factors associated with clinical responses were analyzed using a multivariate permutation test, and survival outcomes were determined using Kaplan-Meier and log-rank tests.

Results: A training set from 10 patients identified 68 potentially relevant soluble factors that were then tested in an independent validation set of 49 patients. Class comparison revealed a cluster of 11 biomarkers that were associated with therapeutic outcome. Vascular endothelial growth factor (VEGF) and fibronectin were identified as independent predictors of response. In particular, high levels of these proteins were correlated with lack of clinical response and decreased overall survival.

Conclusion: Serum VEGF and fibronectin are easily measured pretreatment biomarkers that could serve to exclude patients unlikely to respond to IL-2 therapy.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / blood*
  • Carcinoma, Renal Cell / blood
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / secondary
  • Cluster Analysis
  • Female
  • Fibronectins / blood*
  • Humans
  • Interleukin-2 / therapeutic use*
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Male
  • Melanoma / blood
  • Melanoma / drug therapy*
  • Melanoma / mortality
  • Melanoma / secondary
  • Middle Aged
  • Patient Selection
  • Predictive Value of Tests
  • Prospective Studies
  • Proteomics
  • Recombinant Proteins / therapeutic use
  • Reproducibility of Results
  • Risk Assessment
  • Skin Neoplasms / blood
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Time Factors
  • Treatment Failure
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / blood*
  • Young Adult


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Fibronectins
  • IL2 protein, human
  • Interleukin-2
  • Recombinant Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A