Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients

Ann Oncol. 2007 Feb;18(2):226-32. doi: 10.1093/annonc/mdl158. Epub 2006 Nov 20.

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been and is still widely used as an adjuvant in clinical trials of vaccination with autologous tumor cells, peptides and/or dendritic cells in a variety of human neoplasms. This cytokine was administered either as product of gene-transduced tumor cells or as recombinant protein together with the vaccine given subcutaneously or intradermally. Results of these trials were heterogeneous in terms of induction of vaccine-specific immune response and of clinical response. Though in some of these studies GM-CSF appeared to help in generating an immune response, in others no effect or even a suppressive effect was reported. Here, we review the literature dealing with the immune adjuvant activity of GM-CSF both in animal models and clinical trials. As a consequence of such analysis, we conclude that GM-CSF may increase the vaccine-induced immune response when administered repeatedly at relatively low doses (range 40-80 microg for 1-5 days) whereas an opposite effect was often reported at dosages of 100-500 microg. The potential mechanisms of the GM-CSF-mediated immune suppression are discussed at the light of studies describing the activation and expansion of myeloid suppressor cells by endogenous tumor-derived or exogenous GM-CSF.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Cancer Vaccines / administration & dosage*
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Humans
  • Neoplasms / immunology*
  • Neoplasms / therapy

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Granulocyte-Macrophage Colony-Stimulating Factor