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Annals of Oncology Advance Access published online on November 20, 2006
Annals of Oncology, doi:10.1093/annonc/mdl158
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© 2006 European Society for Medical Oncology
Received May 18, 2006
Accepted May 29, 2006

review

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

G. Parmiani 1 *, C. Castelli 1, L. Pilla 1, M. Santinami 2, M. P. Colombo 3, and L. Rivoltini 1

1 Unit of Immunotherapy of Human Tumors, Department of Innovative Therapies, Istituto Nazionale Tumori, Milan, Italy
2 Unit of Melanoma/Sarcoma Surgery, Department of Surgery, Istituto Nazionale Tumori, Milan, Italy
3 Unit of Immunotherapy and Gene Therapy, Istituto Nazionale Tumori, Milan, Italy

* To whom correspondence should be addressed.
G. Parmiani, E-mail: giorgio.parmiani{at}istitutotumori.mi.it


  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.

Keywords: adjuvant; GM-CSF; immune stimulation; immune suppression.
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