In vivo cytokine production and recombinant interleukin 2 immunotherapy: an insight into the possible mechanisms underlying clinical responses

Br J Cancer. 1994 Jun;69(6):1130-5. doi: 10.1038/bjc.1994.222.

Abstract

Recombinant interleukin 2 (rIL-2), when given to patients with advanced malignant disease, induces a limited beneficial effect, with only 20-30% of patients with solid tumours responding. This present study has identified those patients with advanced colorectal cancer most likely to respond to rIL-2 therapy, by analysis of serum cytokine levels, prior to and during rIL-2 treatment, documented in responders and non-responders. Responders were found to have significantly lower pretreatment serum IL-6 and soluble IL-2 receptor levels (sIL-2R) than non-responders (P < 0.01 and P < 0.05 respectively). During rIL-2 infusion, responders developed high circulating levels of IL-6 and had low constant levels of prostaglandin E2 (PGE2). Non-responders failed to produce IL-6 and demonstrated elevated serum concentrations of PGE2, during infusions of rIL-2. Thus, an enhanced ongoing IL-6 and sIL-2R response, prior to therapy, was detrimental to subsequent treatment with rIL-2. Differential production and/or release of cytokines and prostaglandins, during therapy, further determined the likelihood of response to rIL-2.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Cytokines / blood*
  • Dinoprostone / blood
  • Humans
  • Immunotherapy*
  • Infusions, Intravenous
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / therapeutic use*
  • Interleukin-6 / blood*
  • Neoplasm Staging
  • Prognosis
  • Receptors, Interleukin-2 / analysis
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use

Substances

  • Biomarkers
  • Cytokines
  • Interleukin-2
  • Interleukin-6
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • Dinoprostone