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

Giorgio Parmiani, C. Castelli, L. Pilla, M. Santinami, M. P. Colombo, L. Rivoltini

Research output: Contribution to journalArticle

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 μg for 1-5 days) whereas an opposite effect was often reported at dosages of 100-500 μg. 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.

Original languageEnglish
Pages (from-to)226-232
Number of pages7
JournalAnnals of Oncology
Volume18
Issue number2
DOIs
Publication statusPublished - Feb 2007

Keywords

  • Adjuvant
  • GM-CSF
  • Immune stimulation
  • Immune suppression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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